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<ul><li>Overview of the Course & Syllabus </li></ul><ul><li>Studying the Brain and Behavior </li></ul><ul><ul><li>•  Disci...
Professor :  James R. Moyer, Jr., Ph.D.   Semester  :  Fall 2010 Office :    Garland 208   Meeting Time : MW 9:00 – 9:50 a...
Determination of Your Final Grade Your overall grade will be determined by combining your scores from the following: 1. Di...
Make-up, Curving and Extra Credit Make-up exam.   Should a student fail to take one of the three scheduled exams   during ...
Getting Help If you are having difficulties or have questions, please do not hesitate to come in for a visit to discuss an...
Studying the Brain and Behavior <ul><li>•  Neuroscience   – multidisciplinary approach to studying the brain </li></ul><ul...
History of Brain Research CARDIOCENTRIC   explanations of behavior prevailed in ancient cultures •  argued that the heart ...
Holism vs. Localization Controlled experiments involving the brain were quite rare until the 19th century.  •  Thus, two s...
1861 – Paul Broca   examined patient “Tan” who had a stroke ~20 yrs earlier.
1876 – David Ferrier   stimulated the motor cortex of monkeys and demonstrated that the indicated areas controlled movemen...
TOPOGRAPHICAL ORGANIZATION - Motor Cortex
TOPOGRAPHICAL ORGANIZATION - Motor Homunculus
TOPOGRAPHICAL ORGANIZATION - Somatosensory Cortex
TOPOGRAPHICAL ORGANIZATION - Somatosensory Cortex
<ul><li>1929 – Karl Lashley   claimed to have evidence supporting holism </li></ul><ul><li>He postulated the following: </...
<ul><li>1940s and 50s – Wilder Penfield   used a 3-Volt battery attached to a probe, he stimulated different areas of the ...
PET scans reveal which specific brain regions are activated by a given task
PET scans reveal which specific brain regions are activated by a given task   Sight Sound Touch Speech
PET scans reveal which specific brain regions are activated by a given task   Sight Sound Touch Speech
PET scans reveal which specific brain regions are activated by a given task   Sight Sound Touch Speech
PET scans reveal which specific brain regions are activated by a given task   Sight Sound Touch Speech
WHERE’S THE MIND? Two schools of thought: Dualism  – the mind and body (or brain) are separate. e.g.,   Plato   “father of...
Physiological Approaches to Consciousness •  Consciousness   can be altered by changes in brain chemistry and thus we may ...
Physiological Approach to Consciousness <ul><li>Blindsight   – ability of person who cannot see objects in their blind fie...
An explanation of the blindsight phenomenon
MRIs of human brain showing corpus callosum (cc) corpus callosum
Identification of an object by smell in a split-brain patient
Identification of an object by sight in a split-brain patient
Angular Gyrus Activity and the Out of Body Experience
END – Lecture 01
ORGANIZATION OF THE NERVOUS SYSTEM •  CNS vs. PNS THE CENTRAL NERVOUS SYSTEM I •  Meninges, Ventricles, and Cerebrospinal ...
Organization of the Nervous System <ul><li>Central Nervous System or CNS   </li></ul><ul><ul><ul><li>•  brain </li></ul></...
The Meninges Line and Protect the CNS <ul><li>3 Layers: </li></ul><ul><li>dura mater   – tough outer layer </li></ul><ul><...
Ventricles & Flow of CSF •  Lateral ventricle (2) •  Third ventricle –  aqueduct of Sylvius •  Fourth ventricle –  central...
Flow of CSF (Choroid Plexus Produces CSF) * * * * * * •  CSF flows from  choroid plexus  (cells that make CSF) •  CSF vol ...
Different Views of the Ventricles & Flow of CSF
CSF Flows Down Spinal Cord  via the  Central Canal
 
<ul><li>5 Segments of the Spinal Cord </li></ul><ul><li>Cervical </li></ul><ul><li>Thoracic </li></ul><ul><li>Lumbar </li>...
Anatomical Planes
Anatomical Planes
Anatomical Planes
Anatomical Directions
END – Lecture 02
<ul><li>THE CENTRAL NERVOUS SYSTEM II </li></ul><ul><li>The Brain </li></ul><ul><ul><li>•  Forebrain ( prosencephalon ) </...
3 Major Divisions of the Brain <ul><li>Prosencephalon  ( Forebrain ) </li></ul><ul><ul><li>•  telencephalon   (cerebrum, l...
<ul><li>Prosencephalon  ( Forebrain ) – thinking, creating, speaking,  </li></ul><ul><li>planning, emotions, etc… ( pretty...
The Cerebrum Central Sulcus  separates frontal ( precentral gyrus ) from parietal ( postcentral gyrus ) Sylvian Fissure  o...
The Major Lobes of the Cerebrum The Cerebrum
<ul><li>Frontal lobes </li></ul><ul><ul><ul><li>•  motor cortex ,  premotor cortex ,  prefrontal cortex </li></ul></ul></u...
<ul><li>The Cerebral Hemispheres are Connected by: </li></ul><ul><li>Corpus Callosum  – connects left and right frontal, p...
Cross Section through the Cerebrum
The Cerebrum Anterior Commissure Note that the line from the label “Cerebral Cortex” at the upper left seems to point to w...
Diffusion Tensor Imaging of Corpus Callosum Projections Diffusion Tensor Imaging involves a modified MRI magnet.  It enabl...
<ul><li>Prosencephalon  ( Forebrain ) – thinking, creating, speaking,  </li></ul><ul><li>planning, emotions (pretty much a...
Limbic System  – a circuit of structures involved in emotion and memory (Paul MacLean, 1949) <ul><li>Hippocampus </li></ul...
Schematic of Limbic Structures
Superior View of Limbic Structures Side View of Limbic Structures (without any other brain regions)
<ul><li>Prosencephalon  ( Forebrain ) – thinking, creating, speaking,  </li></ul><ul><li>planning, emotions (pretty much a...
Basal Ganglia  – a cluster of neuronal structures concerned with the  production of movement. <ul><li>Putamen and Globus P...
Location of the Basal Ganglia & Thalamus
<ul><li>Prosencephalon  ( Forebrain ) – thinking, creating, speaking,  </li></ul><ul><li>planning, emotions (pretty much a...
Diencephalon  – forebrain region that surrounds the 3rd ventricle <ul><li>Thalamus </li></ul><ul><ul><ul><li>•  a large nu...
Thalamic Connections with the Cortex
Thalamic Connections using Diffusion Tensor Imaging
Location of the Hypothalamus & Pituitary Gland
Location of the Hypothalamus & Pituitary Gland
3 Major Divisions of the Brain <ul><li>Prosencephalon  ( Forebrain ) </li></ul><ul><ul><li>•  telencephalon  (cerebrum, li...
<ul><li>Mesencephalon  ( Midbrain ) – also contains the reticular formation which runs from hindbrain to forebrain </li></...
3 Major Divisions of the Brain <ul><li>Prosencephalon  ( Forebrain ) </li></ul><ul><ul><li>•  telencephalon  (cerebrum, li...
<ul><li>Rhombencephalon  ( Hindbrain ) – immediately superior to spinal cord  </li></ul><ul><ul><li>1.  Cerebellum   </li>...
Midsagittal view of  Forebrain, Midbrain, & Hindbrain
Parts of the Forebrain, Midbrain, & Hindbrain
Human Brainstem
END – Lecture 03
<ul><li>DIVISIONS OF THE PERIPHERAL NERVOUS SYSTEM  </li></ul><ul><li>Somatic vs. Autonomic </li></ul><ul><li>Sympathetic ...
Divisions of the Peripheral Nervous System <ul><li>Somatic Nervous System   </li></ul><ul><ul><ul><li>•  controls skeletal...
Divisions of the Autonomic Nervous System <ul><li>Sympathetic Nervous System   </li></ul><ul><ul><ul><li>•  fight-or-fligh...
Divisions of the Autonomic Nervous System <ul><li>Eyes </li></ul><ul><li>Lungs </li></ul><ul><li>Heart </li></ul><ul><li>S...
PNS Transmits Information to the Body via 43 Pairs of Nerves •  12 pairs of  CRANIAL NERVES   –  enter & exit the brain th...
CRANIAL NERVES (12 pairs, CNs I through XII) •  enter & exit the brain through holes ( foramena ) in skull •  permit direc...
CRANIAL NERVES (12 pairs) 3 of the cranial nerves serve sensory functions only: •  CN I (olfactory nerve) –  sensory ; sme...
Red is motor Blue is Sensory
CRANIAL NERVES (12 pairs) 3 of the cranial nerves control eye movement: •  CN I (olfactory nerve) –  sensory ; smell •  CN...
Red is motor Blue is Sensory
CRANIAL NERVES (12 pairs) 2 of the cranial nerves control facial muscles: •  CN I (olfactory nerve) –  sensory ; smell •  ...
Red is motor Blue is Sensory
CRANIAL NERVES (12 pairs) 2 of the cranial nerves control throat and tongue muscles: •  CN I (olfactory nerve) –  sensory ...
Red is motor Blue is Sensory
CRANIAL NERVES (12 pairs) 1 cranial nerve wanders to the head, neck, & upper abdomen: •  CN I (olfactory nerve) –  sensory...
Red is motor Blue is Sensory
CRANIAL NERVES (12 pairs) 1 cranial nerve is motor only & innervates neck muscles: •  CN I (olfactory nerve) –  sensory ; ...
Red is motor Blue is Sensory
The Cranial Nerves &  Their Functions Bell’s Palsy  –  facial paralysis caused by an infection of the  facial nerve  ( CN ...
PNS Transmits Information to the Body via 43 Pairs of Nerves •  12 pairs of  CRANIAL NERVES   –  enter & exit the brain th...
Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra
Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra
Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra
Cross Section of Spinal Cord <ul><li>Sensory is Dorsal (signals enter) </li></ul><ul><li>Motor is Ventral (signals exit th...
SPINAL NERVES (31 pairs) •  enter & exit the spinal cord between vertebrae •  8 pairs arise from  Cervical  region ( C1–C8...
<ul><li>5 Segments of the Spinal Cord </li></ul><ul><li>Cervical </li></ul><ul><li>Thoracic </li></ul><ul><li>Lumbar </li>...
Dermatome Map •  The body area innervated by one spinal nerve Q: Why do you not see C1 on the dermatome map to the right?
Sacral–Parasympathetic (anus, genitals, & bladder) Cranial–Parasympathetic (organs, vessels, and  muscles, etc…) Thoracic ...
•  thoracolumbar •  craniosacral Distribution of the Autonomic Nervous System
END – Lecture 04
<ul><li>NEURONS AND GLIAL CELLS </li></ul><ul><li>Structure of Neurons </li></ul><ul><ul><ul><li>•  Soma </li></ul></ul></...
The Nervous System Two Types of Cells: 1.  Neurons  – cells of the nervous system 2.  Glia  – support cells Historically: ...
3 Parts of a Neuron   <ul><li>Soma  or cell body (contains nucleus, etc…) </li></ul><ul><li>Dendrite  (transmits signals t...
Example of a Motor Neuron
Parts of a Neuron
Information Flow Between and Within Neurons   1. Signal enters dendrite or soma 2. Signal travels from soma to axon 3. Sig...
Divergence (e.g., sensory)  Convergence (e.g., motor)   Information Flow Between Neurons
Basic Subcellular Components of Mammalian cells  (similar for neurons)
Structure of Neurons
Major Organelles <ul><li>Nucleus  – contains DNA.  Gene expression occurs by transcription of DNA into RNA, which is expor...
Cell Nucleus and Protein Synthesis Chromosomes   contain genetic information, 23 pairs –  22 pairs are   autosomal –  the ...
Structure of Neurons
Examples of Genetic Alterations that affect Brain Function Fragile-X Syndrome –  normally the X chromosome (FMR1 gene has ...
Classifying Neurons 1. Based on anatomical or morphological features (Ramón y Cajal) –  unipolar (or monopolar) neuron –  ...
Anatomical Classifications
Example of a Sensory Neuron   Note: functionally, this pseudo-unipolar cell contains one axon (on the left) and a sensory ...
Functional Classifications <ul><li>Motor neuron </li></ul><ul><li>Sensory neuron </li></ul><ul><li>Interneuron </li></ul>
Functional Classifications <ul><li>Motor neuron </li></ul><ul><li>Sensory neuron </li></ul><ul><li>Interneuron </li></ul>B...
Glial Cells <ul><li>“ glue ” that holds the nervous system together </li></ul><ul><li>There are   10 times   as many glial...
Roles of Glial Cells in the Nervous System <ul><li>Provide nourishment for neurons </li></ul><ul><ul><ul><li>Astrocytes su...
Glial Cells – Astrocytes
Myelination of Axons Schwann Cells  (PNS) Oligodendrocytes  (CNS) Value of myelination: 1. Speeds axonal transmission (act...
Electron Micrograph of a Schwann Cell Schwann Cells –   myelinate only one segment of one axon
Comparison of Oligodendrocytes and Schwann Cells
Oligodendrocytes myelinate multiple segments of multiple axons
Blood-Brain Barrier
Blood-Brain Barrier
END – Lecture 05
Parts of a Cell Slides <ul><li>These slides contain background information the majority of which you are expected to know ...
Structure of Neurons
Major Organelles <ul><li>Nucleus – contains DNA.  Gene expression occurs by transcription of DNA into RNA, which is export...
Cell Nucleus and Protein Synthesis Chromosomes  contain genetic information, 23 pairs –  22 pairs are  autosomal –  the fi...
Structure of Neurons
Examples of Genetic Alterations that affect Brain Function Fragile-X Syndrome –  normally the X chromosome (FMR1 gene has ...
<ul><li>How Do Neurons Communicate? </li></ul><ul><ul><ul><li>•  chemical & electrical transmission </li></ul></ul></ul><u...
How Do Neurons Communicate? <ul><li>Chemical Transmission </li></ul><ul><ul><li>•  Releasing chemicals onto another neuron...
Synapse  – the junction between two connected neurons  (Sherrington, 1906)  Synapse  is composed of: 1.  presynaptic  memb...
Electron Micrograph of an axodendritic synapse
EM of axodendritic synapse Mag: 280,000 X
Types of Synapses in the Nervous System <ul><li>Axodendritic </li></ul><ul><ul><li>–  onto dendrites (a) </li></ul></ul><u...
How Do Neurons Communicate? <ul><li>Chemical Transmission </li></ul><ul><ul><li>•  Releasing chemicals onto another neuron...
Glial Cells and Neurons can communicate via Gap Junctions Gap junctions  – enable electrical coupling between neurons and/...
Resting Membrane Potential (RMP) •  Neurons are bathed in a salt solution (the salts dissociate into ions) •  Ions are pos...
 
Recording Neuronal Activity Much of what we know about the ionic basis of membrane potential and the action potential was ...
Recording Neuronal Activity
Neuronal Cell Membrane is a Phospholipid Bilayer with Ion Channels Ions (salts) cannot simply diffuse across the cell memb...
High Na +   and   Cl -  outside (low inside)  High K +  inside (low outside) Distribution of Ions Across the Neuronal Memb...
What is the Equilibrium or Reversal Potential of an Ion?
Distribution of Ions Across the Neuronal Membrane at Rest 2 forces at work:  chemical and electrical gradients
At Rest During Depolarization •  Neuron’s RMP is negative at rest •  During depolarization, Na +  rushes into cell, making...
•  Small inputs are  subthreshold  (e.g., 1, 2, 3) •  If input is large enough, threshold is reached. •  At threshold, an ...
Summary of Ion Channel Activity During an Action Potential
Summary of Ion Flow During an Action Potential <ul><li>Na +   influx </li></ul><ul><li>K +  efflux </li></ul><ul><li>Overs...
Conduction of the Action Potential
Movement of an Action Potential down an Unmyelinated Axon
Action Potential Propagation <ul><li>Na +  influx </li></ul><ul><li>K +  efflux </li></ul><ul><li>Spread of depolarization...
Saltatory Conduction – conserves energy; increases conduction speed (up to 120 m/s or 432 km/hr) Myelination
Saltatory Conduction IMPORTANT CONCEPTS: •  Distribution of Na +  & K +  channels •  Spread of electrical charge
Action Potential Propagation THOUGHT QUESTION: Is it better to have a previously myelinated axon become demyelinated or is...
The Na-K Pump ( 3 Na +   :  2K + ) also called the  Na-K ATPase Summary of Action Potential Events 1. During AP, Na +  ent...
Coding of Stimulus Strength
1.  Temporal summation 2.  Spatial summation How does a neuron integrate or add up inputs it receives?
Temporal and Spatial summation
Temporal and Spatial summation
END – Lecture 06
PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 07  (September 29, 2010) <ul><li>Ion Channels </li></ul><ul><ul><ul><li>•  liga...
Four General Classes of Ion Channels
Movement of Sodium Ions with Channel Opening
Basic Steps involved in Transmitter Release
Before  the action potential arrives, the  postsynaptic   ligand-gated channels  are  closed After  the action potential a...
Schematic of Synaptic Vesicle Release
Steps Involved in Neurotransmitter Release
Neurotransmitter Release & Reuptake
EM of Synaptic Vesicle Release
Summary of Steps Involved in Neurotransmitter Release <ul><li>Action Potential Arrives  at axon terminal (Na +  influx) </...
Membrane Recycling is Essential <ul><li>Synaptic vesicle fusion </li></ul><ul><li>Pinocytosis of membrane </li></ul><ul><l...
<ul><li>Concentration gradient of Na +  (more out than in) means that  Na +  ions flow  INTO  the cell (and  influx of pos...
Movement of Major Ions (EPSPs vs IPSPs)
Postsynaptic and Presynaptic Inhibition Simple Rule of Thumb (each causes hyperpolarization of the membrane): Postsynaptic...
Balance between Excitation and Inhibition
2 Types of Ligand-Gated Receptors <ul><li>Ionotropic Receptors  – direct link to ion channel </li></ul><ul><li>Metabotropi...
IONOTROPIC RECEPTORS (e.g., nicotinic AChRs)
<ul><li>Neurotransmitter binds </li></ul><ul><li>G-protein activated </li></ul><ul><li>Adenylate cyclase activated </li></...
METABOTROPIC RECEPTORS Effects of Second Messenger Cascades, such as those through metabotropic G-protein-linked receptors...
Agonists and Antagonists •  Agonist activates the receptor •  Antagonist blocks the receptor
Two Common Types of Agonists and Antagonists DIRECT   INDIRECT Competes for same site  as neurotransmitter ( competitive )...
FIVE WAYS IN WHICH DRUGS CAN AFFECT  SYNAPTIC TRANSMISSION <ul><li>Synthesis of the transmitter ( 1 & 2 ) </li></ul><ul><l...
SUMMARY OF WAYS IN WHICH DRUGS CAN AFFECT SYNAPTIC TRANSMISSION Note:  AGO  = agonist ( blue Box );  ANT  = antagonist ( r...
END – Lecture 07
PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 08 (October 04, 2010) <ul><li>NEUROTRANSMITTER SYSTEMS I </li></ul><ul><li>Neur...
Neurotransmitters and Neurohormones •  Neurotransmitters  – substances released by one neuron that bind to  receptors on t...
Neurohormone Release of epinephrine from the adrenal gland produces  sympathetic arousal
Examples of Neurotransmitters in the Brain <ul><li>Acetylcholine  </li></ul><ul><li>Dopamine  </li></ul><ul><li>Norepineph...
Neurotransmitter Associated Neurons Acetylcholine cholinergic Dopamine dopaminergic Norepinephrine noradrenergic Serotonin...
Acetylcholine •  First neurotransmitter discovered (in PNS) •  Most extensively studied neurotransmitter
Cholinergic Neurons 1. Dorsolateral Pons ––––––– REM sleep (including atonia) 2. Basolateral Forebrain –––– Activates cere...
Synthesis of Acetylcholine Produced by combining the lipid breakdown product  choline   with  acetyl-CoA   (made in the mi...
Synthesis of Acetylcholine
Enzymes Enzymes are proteins that catalyze a reaction that might normally take a long time to occur. If you see a word end...
Two Types of ACh Receptors <ul><li>Ionotropic  –––  Nicotinic AChRs (fast) </li></ul><ul><li>Metabotropic –  Muscarinic AC...
Cholinergic Receptors •  Muscles contain  nicotinic AChRs   ( essential for rapid transmitter action at neuromuscular junc...
Breakdown & Local Synthesis of ACh Acetylcholinesterase  – Inactivates ACh after it is released (AChE)     (breaks it into...
Breakdown & Local Synthesis of ACh
Acetylcholinesterase ( located in the synaptic cleft ) breaks down acetylcholine into acetate and choline (which is recycl...
Drugs that Affect Cholinergic Receptors Examples 1. Curare •  Blocks nicotinic AChRs (or nAChRs)  •  Had been and still is...
Toxins that Affect Cholinergic Transmission Examples 1. Botulinum toxin  –––––––––––––  Clostridium botulinum Prevents rel...
Drugs that Affect ACh Breakdown Acetylcholinesterase inhibitors  (AChE inhibitors) •  Prolong the effects of ACh release b...
Summary of Cholinergic Drugs Drug Name     Drug Effect     Effect on Transmission Nicotine Stim nicotinic AChRs AGONIST Cu...
Classification of the Monoamine Transmitters Catecholamines Indolamines Dopamine Serotonin Norepinephrine Epinephrine
Synthesis of dopamine  (note DA serves as a precursor for norepinephrine) <ul><li>Tyrosine hydroxylase </li></ul><ul><li>D...
Dopaminergic Neurons & Projections 1. Substantia Nigra  –––––––––  to  neostriatum , part of basal ganglia   (involved in ...
 
MAO (Monoamine Oxidase) –  destroys excess monoamines –  MAO-B is specific for dopamine –  Deprenyl is an MAO-B inhibitor ...
Drugs that Affect Dopaminergic Transmission Examples 1. Monoamine oxidase inhibitors  (MAO inhibitors) •  MAO regulates pr...
Examples of Drugs that Affect Dopaminergic Transmission 1. L-DOPA •  Used to treat Parkinson’s disease •  Crosses blood-br...
Effects of Drugs at Dopaminergic Synapses
Dopamine Receptors •  DA receptors are  metabotropic •  5 subtypes of DA receptors (D1 – D5)  - D1 & D2 are the most commo...
Schizophrenia •  Serious mental disorder characterized by hallucinations, delusions, and disruption of normal logical thou...
Summary of Dopaminergic Drugs Drug Name   Drug Effect     Effect on Transmission L-DOPA Stimulate DA synthesis AGONIST AMP...
Noradrenergic Neurons Locus Coeruleus  (located in Reticular Formation)  •  Contains noradrenergic neurons whose axons ext...
Norepinephrine •  Synthesized from dopamine •  Synthesis actually occurs inside synaptic vesicles
Synthesis of dopamine and norepinephrine Add  –CH 3  to the NH 2  group  to get epinephrine <ul><li>Tyrosine hydroxylase <...
Examples of Drugs that Affect Noradrenergic Transmission 1. Fusaric acid •  Blocks DA-  -hydroxylase •  Results in blocka...
Noradrenergic Receptors •  NE receptors are called  adrenergic   because they respond to both norepinephrine (nor adren al...
 
Summary of Noradrenergic Drugs Drug Name   Drug Effect       Effect on Transmission Clonidine  – has a calming effect (but...
END – Lecture 08
PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 09 (October 06, 2010) <ul><li>NEUROTRANSMITTER SYSTEMS II </li></ul><ul><li>The...
Serotonin •  Synthesized from the amino acid  tryptophan •  Important in the following: -  regulation of  mood -  control ...
Serotonin • PRECURSORS to serotonin  Dorsal Raphe –– sends 5-HT projections to cortex & basal ganglia •  Medial Raphe –– s...
Synthesis of Serotonin (or 5-HT) PCPA ( p -chlorophenylalanine) •  blocks tryptophan hydroxylase and thus serotonin  produ...
Serotonin Receptors •  5-HT receptors are metabotropic ( except  5-HT 3  is an ionotropic Cl -  channel ) •  At least 9 di...
Drugs that Affect Serotonin •  5-HT re-uptake inhibitors ( SRIs  or  SSRIs ) are useful in treating certain mental disorde...
Summary of Serotonergic Drugs Drug Name   Drug Effect     Effect on Transmission Fenfluramine Stimulate 5-HT release AGONI...
Summary of Neurotransmitter Synthesis Pathways PKU (phenylketonuria) - myelination - brain damage
Amino Acid Neurotransmitters Two Major Classes:  excitatory  and  inhibitory 1. The Excitatory Neurotransmitter is  Glutam...
Amino Acid Neurotransmitters <ul><li>GLUTAMATE  (PRINCIPLE EXCITATORY TRANSMITTER) </li></ul><ul><li>•  4 receptor subtype...
NMDA Receptor Channel Complex 6 NMDAR Binding Sites 1.  Glutamate  (natural agonist) 2. Glycine  (co-agonist required for ...
Amino Acid Neurotransmitters GABA  (MAJOR INHIBITORY TRANSMITTER IN BRAIN) •  2 main receptor subtypes ( 1 ionotropic  &  ...
GABA Receptors •  Enzyme  GAD  (glutamic acid decarboxylase) converts  glutamic acid   to  GABA   - GAD is inhibited by al...
GABA A  Receptors GABA A  Receptor has 5 binding sites 1.  GABA   (natural agonist) •  muscimol is a direct agonist •  bic...
Other  Neurotransmitters / Neuromodulators <ul><li>Peptides </li></ul><ul><ul><li>•  2 or more amino acids linked together...
END – Lecture 09
PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 10 (October 13, 2010) <ul><li>PLASTICITY IN THE NERVOUS SYSTEM </li></ul><ul><l...
Development of the Human Brain Relative Brain Size: At birth: ~  350 g At 1 yr:  ~1000 g Adult:  ~1200 g •  Forebrain •  M...
Timeline of Major Stages in Cerebral Cortex Development Neurogenesis  declines significantly by week 20 and is nearly comp...
Origin of Brain Cells Neurotrophic factors •  EGF   (epidermal growth factor) –  stem to progenitor •  bFGF   (basic fibro...
Brain Development <ul><li>Processes involved in neuron production : </li></ul><ul><li>Proliferation  </li></ul><ul><ul><ul...
Axon Pathfinding (how does an axon know where to go?) Roger Sperry (1943)
Axon Growth and Neuron Survival Growth Cones extend out as axons seek targets Tropic molecules  guide axons; produced by t...
Synapse Pruning (Elimination) Synaptic connections are plastic!
Effect of Experience on Plasticity  <ul><li>Environmental Enrichment </li></ul><ul><ul><li>•  Increases  dendrite complexi...
Regrowth of Axons  •  Can occur as long as the soma or cell body is intact •  Rate is usually  ~1 mm/day (PNS) •  in CNS, ...
Collateral Sprouting
Denervation Supersensitivity Remember: Amphetamine causes DA release from existing axon terminals Apomorphine stimulates D...
END – Lecture 10
<ul><li>MUSCLES & SPINAL REFLEXES </li></ul><ul><li>Muscle Cell Types and Muscle Fibers </li></ul><ul><li>Skeletal Muscles...
Muscles and Muscle Fibers
3 Types Muscle
Muscles  and Muscle Fibers Skeletal Muscle : •  Attach to bone or cartilage via tendons •  Made up of cells (muscle fibers...
Major Components of Skeletal Muscle
Skeletal Muscle : •  Striated appearance due to arrangement of actin & myosin •  Actin  filaments (thin)  are attached to ...
Sliding Filament Theory
Neuromuscular Junction & Muscle Contraction : •  Motor neurons innervate skeletal muscle fibers at a special region called...
Classification of Skeletal Muscles by Color : Red Muscle  –  High concentration of myoglobin (carries oxygen) –  Relies he...
Antagonistic Muscles (flexion and extension) Isotonic Contraction (muscle shortens) e.g., legs, produces the movement when...
Opposing or Antagonistic Muscle Movements Antagonistic Muscles (flexion vs extension)
Spinal Control of Movement REFLEXES  are rapid movements mediated by either brain stem nuclei or the  spinal cord  (we’ll ...
Three Reflexes Seen in Infants •  Grasping •  Babinski •  Rooting
The Babinski Reflex –  in children & adults it’s diagnostic of CNS damage •  Positive   Babinski   – fanning of toes with ...
Withdrawal Reflex is a simple  reflex  involving only  a few synapses  between the sensory (afferent) neuron and the motor...
Withdrawal Reflex  (involves one or more interneurons between the sensory and motor neuron) Note: the more interneurons (a...
Withdrawal Reflex Note: descending projections from the brain can inhibit reflexes
2 Types of Motor Neurons <ul><li>Alpha motor neurons </li></ul><ul><ul><ul><li>•  larger diameter </li></ul></ul></ul><ul>...
Extrafusal   fibers run the length of the muscle Intrafusal   fibers do not run the length of the muscle and are located w...
Examples •  Patellar tendon reflex •  Head bobbing upward when falling asleep while sitting in a chair Monosynaptic Stretc...
Intrafusal muscle fibers Muscle Spindle  – A few intrafusal fibers joined to a  nuclear bag  (inside the nuclear bag is a ...
Gamma Motor Neurons Notice that if the muscle length changes due to muscle contraction  (b) , the muscle spindle is “off l...
Problem inherent in the stretch reflex •  Contraction of one muscle would produce contraction of antagonist muscle •  For ...
Reciprocal Innervation Prevents the simple bending of an arm (biceps contraction) from causing the arm to straighten due t...
What if the muscle is contracting too vigorously? Golgi Tendon Organ Reflex  is activated Golgi Tendon Organ (GTO)  –  str...
Golgi Tendon Organ Reflex Think of the GTO like a “spring” located at each end of the muscle (in the tendon)
Proprioceptors (stretch receptors)
Sir Charles Scott Sherrington  (1884-1935) •  Studied many kinds of reflexes •  Discovered  reciprocal innervation •  Intr...
Crossed Extensor Reflex •  Withdrawal Reflex  activated by sensory neuron synapsing onto interneuron, which excites motor ...
END – Lecture 11
<ul><li>CONTROL OF MOVEMENT BY THE BRAIN </li></ul><ul><li>Anatomical Considerations </li></ul><ul><ul><ul><li>•  upper & ...
Classification of Neurons Associated with the Motor System <ul><li>Upper Motor Neurons   </li></ul><ul><ul><ul><li>•  abov...
Motor Cortex & Motor Homunculus 1 2 3 4
Classification of Descending Motor Systems <ul><li>The Lateral Group or System  ( fine or directed movements ) </li></ul><...
The Lateral (Pyramidal) Motor System Originates in the Primary Motor Cortex (precentral gyrus) Axons of these Upper Motor ...
Lateral Corticospinal Tract •  fine, directed motor control •  hands, fingers, feet, toes •  synapse  directly  onto motor...
Effects of Damage to Corticospinal Tract Damage to the Corticospinal Tract at any Level  produces: 1. Initial loss of musc...
Effects of Cortical Damage to Lateral System Damage to the Premotor or Supplementary Motor Cortex or to parts of the Parie...
Cortical Control of Movement Posterior association cortex  is   involved with perceptions Frontal association cortex  is  ...
Motor Neuron Disorders Muscular Dystrophy  – muscle wasting •  30 different types, Duchenne’s MD is the most common  - abo...
The Medial (Extrapyramidal) Motor System Coordinates gross movements & postural adjustments •  Develops before the pyramid...
The Medial (Extrapyramidal) Motor System <ul><li>Brain Regions </li></ul><ul><li>Cerebellum </li></ul><ul><ul><ul><li>•  R...
The Cerebellum and Movement Note: The cerebellum may contain ~50 billion neurons, compared with ~22 billion neurons in the...
Basal Ganglia  – a cluster of neuronal structures concerned with the production of movement. <ul><li>Striatum  ( Caudate ,...
Location of the Basal Ganglia within the Forebrain
Damage to the Basal Ganglia Basal ganglia damage results in movement disorders Tics  – brief, involuntary contractions of ...
Relationship Between CAG Repeats and Age of Onset •  CAG codes for glutamine •  11-24 CAG repeats is normal •  >36 is link...
Brain of Patient with Huntington’s Disease
Treatments for Parkinson’s Disease 1. Pharmacological Treatments L-DOPA – crosses blood-brain barrier and is converted to ...
END – Lecture 12
<ul><li>THE VISUAL SYSTEM I </li></ul><ul><li>Electromagnetic Spectrum & Waves </li></ul><ul><li>Anatomy of the Eye </li><...
Many Stimuli are Transmitted as Waves  (e.g., electromagnetic radiation, vibration, and sound) The Electromagnetic Spectru...
v  = ƒ    Electromagnetic Radiation (e.g., Light Waves) Relationship between  velocity ( v ) ,   frequency (ƒ) , and  wav...
Stimulus Intensity is encoded by changes in  action potential frequency Adaptation  is a decrease in the firing rate in re...
Distribution of Visual Receptors Why is this baby owl’s head nearly upside down?
The Visual System
The
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  1. 1. <ul><li>Overview of the Course & Syllabus </li></ul><ul><li>Studying the Brain and Behavior </li></ul><ul><ul><li>• Disciplines & Approaches </li></ul></ul><ul><li>History of Brain Research </li></ul><ul><ul><li>• Cardiocentric vs. Encephalocentric </li></ul></ul><ul><ul><li>– Hippocrates, Aristotle, Galen, Descartes </li></ul></ul><ul><ul><li>• Holism vs. Localization </li></ul></ul><ul><li>Development of Brain Research </li></ul><ul><ul><li>• Topographical Organization </li></ul></ul><ul><ul><li>• Lashley’s Law of Mass Action </li></ul></ul><ul><ul><li>• Brain Mapping </li></ul></ul><ul><ul><li>• Dualism vs. Monism </li></ul></ul><ul><li>Physiological Approach to Consciousness </li></ul><ul><ul><li>• Blindsight </li></ul></ul><ul><ul><li>• Split Brains </li></ul></ul><ul><ul><li>• Unilateral Neglect </li></ul></ul>PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 01 (September 08, 2010)
  2. 2. Professor : James R. Moyer, Jr., Ph.D. Semester : Fall 2010 Office : Garland 208 Meeting Time : MW 9:00 – 9:50 a.m. Office hrs: MW 10:00 – 10:50 a.m. Meeting Place : ENG 105 Office ph: x3255 Psych Listing : 254–402 lecture Email: [email_address] Course Description This course is designed to provide each student with comprehensive exposure to the nervous system and how it governs various behaviors . The course will also cover relevant anatomical, behavioral, psychological, cellular, imaging, and neurophysiological approaches used to study animal behavior. Upon completion of the course, the student will have a solid foundation regarding the biological basis of behavior upon which to build in more advanced courses of study. Reading Materials The recommended textbook for this course is Carlson, NR (2010). Physiology of Behavior, 10 th Ed. Allyn & Bacon, New York, NY . (Note: there are a variety of texts on reserve in the library as well). Course Syllabus for Physiological Psychology
  3. 3. Determination of Your Final Grade Your overall grade will be determined by combining your scores from the following: 1. Discussion Section Attendance (10%) . Discussion sessions will begin Monday, September 13. TA will take attendance. If you cannot make your discussion session, you must make arrangements to attend one of the other 9 discussion sections that week . See page 6 of the syllabus for the weekly discussion session schedule . 2. Weekly Online Quizzes (25%) . There will be 12 open-book/notes quizzes available for you to take online beginning September 13 (each quiz will be available for one week). See page 7 of the syllabus for the quiz schedule. NO make-ups (if you fail to take a quiz you will receive a grade of zero for that quiz). 3. Regular Exams (40%). There will be 2 exams ( multiple-choice, true-false, matching questions ) scheduled during the semester (see dates on syllabus). Exams will be cumulative , which means that there will be some material from the previous exam(s) on each successive exam. 4. Final exam (25%). There will be a cumulative final exam on Tuesday, December 21, 2010 from 10:00 a.m. to 12:00 p.m. in ENG 105 . Any student who does not take the final exam will fail the course. The final grade for the course will be determined based on your final average according to the following scale: A = 93-100%; A- = 90-92%; B+ = 87-89%; B = 83-86%; B- = 80-82%; C+ = 77-79%; C = 73-76%; C- = 70-72%; D+ = 67-69%; D = 63-66%; D- = 60-62%; F = 0-59%. Course Syllabus for Physiological Psychology
  4. 4. Make-up, Curving and Extra Credit Make-up exam. Should a student fail to take one of the three scheduled exams during the semester, that student will receive a zero “0” as a grade for that exam. However, at the end of the semester a “one size fits all” cumulative make-up will be offered for students who missed one of the exams (no excuse or reason necessary). The make-up will be held on the study day at 9:00 a.m. on Wednesday, December 15 in ENG 105 . Curving of exams. I will not curve any of the exams. However, all exams will contain some extra credit questions. Thus, it is always possible to score greater than 100% on any exam, including the final. Extra credit. You may receive up to a maximum of 5 extra credit points, which will be added to your final exam score (thus, if you scored an 86% on the final and you did 5 points worth of extra credit, your final exam score would be a 91%). Check bulletin boards in Garland and Pearse for extra credit opportunities. I will also post some extra credit opportunities on the D2L, if an instructor requests an advertisement in class. Course Syllabus for Physiological Psychology
  5. 5. Getting Help If you are having difficulties or have questions, please do not hesitate to come in for a visit to discuss any issues pertinent to your academic success. If you are struggling in the class, don’t wait until you’ve taken numerous quizzes or both exams to come for help . One mistake students often make is waiting too long to come to me to discuss their performance in the class, which limits my ability to help the student. Course Syllabus for Physiological Psychology
  6. 6. Studying the Brain and Behavior <ul><li>• Neuroscience – multidisciplinary approach to studying the brain </li></ul><ul><li>• Behavioral Neuroscience – e.g., psychologists using a bottom-up approach </li></ul><ul><ul><li>• also Physiological Psychology or Biopsychology </li></ul></ul><ul><li>• Cognitive Neuroscience – e.g., psychologists using a top-down approach </li></ul><ul><li>• Neuropsychology – e.g., psychologists ( top-down ) studying higher brain functions and their disorders following brain injury or disease </li></ul><ul><ul><li>• also Clinical Neuropsychology or Experimental Neuropsychology </li></ul></ul><ul><li>• Computational Neuroscience – utilization of mathematical models to explain </li></ul><ul><ul><li>how neuronal activity relates to information processing in the brain </li></ul></ul>
  7. 7. History of Brain Research CARDIOCENTRIC explanations of behavior prevailed in ancient cultures • argued that the heart controlled thoughts, emotions and behavior • e.g., ancient Egyptians removed and discarded the brain before mummification but preserved the heart for the afterlife ENCEPHALOCENTRIC explanations of behavior emerged from dissections • argued that the brain controlled thoughts and emotions and behavior • Hippocrates (460-377 B.C.) after witnessing many dissections argued that the brain controls behavior • Plato (427-327 B.C.) agreed with Hippocrates • Aristotle (384-322 B.C.) disagreed & argued it “cools the heart” • Galen (130-200 A.D.) later concluded that Aristotle’s role for the brain was “utterly absurd” for two reasons: 1. The brain was too far away to cool the heart and 2. Too many sensory nerves were attached to the brain • René Descartes (1596-1650 A.D.) argued that the pineal gland is the seat of the soul and exerts its actions via pressure changes in the fluid-filled ventricles
  8. 8. Holism vs. Localization Controlled experiments involving the brain were quite rare until the 19th century. • Thus, two schools of thought emerged regarding the extent to which specific brain areas govern behaviors. Holism – argued that every area of the brain can control all human functions Localization – argued that human functions are regulated by distinct brain regions • Franz Gall (1757-1828) popularized localization based on his theories that specific brain protuberances (felt via skull) corresponded to specific personality traits “ Phrenology ” • Although not based on experimental evidence, Gall changed how many people thought about the brain and the work of future scientists supported localization of brain function.
  9. 9. 1861 – Paul Broca examined patient “Tan” who had a stroke ~20 yrs earlier.
  10. 10. 1876 – David Ferrier stimulated the motor cortex of monkeys and demonstrated that the indicated areas controlled movement of specific body parts: 1 and 2 hind limbs 3 tail 4, 5, 6 arm a, b, c, d hands and fingers 7-11 face and mouth 12, 13 eyes, head 14 ear 1870 – Fritsch and Hitzig stimulated the motor cortex of dogs and noted that stimulation near the top caused the hind legs to wiggle whereas stimulation near the bottom caused the jaw to move.
  11. 11. TOPOGRAPHICAL ORGANIZATION - Motor Cortex
  12. 12. TOPOGRAPHICAL ORGANIZATION - Motor Homunculus
  13. 13. TOPOGRAPHICAL ORGANIZATION - Somatosensory Cortex
  14. 14. TOPOGRAPHICAL ORGANIZATION - Somatosensory Cortex
  15. 15. <ul><li>1929 – Karl Lashley claimed to have evidence supporting holism </li></ul><ul><li>He postulated the following: </li></ul><ul><li>Law of Mass Action </li></ul><ul><ul><li>• lesion size rather than </li></ul></ul><ul><ul><li>location is what matters </li></ul></ul><ul><li>Law of Equipotentiality </li></ul><ul><ul><li>• restatement of holism </li></ul></ul>
  16. 16. <ul><li>1940s and 50s – Wilder Penfield used a 3-Volt battery attached to a probe, he stimulated different areas of the cortex in awake patients whose brains were exposed (epilepsy surgery). </li></ul><ul><li>He observed the following: </li></ul><ul><li>Recall of memories when back of cortex was stimulated </li></ul><ul><li>Sensations in various body parts in response to topographical stimulation of the somatosensory cortex </li></ul><ul><li>Penfield’s work inspired the drawings of the homunculi which are used to illustrate topographical organization of the primary motor and somatosensory cortices. </li></ul>
  17. 17. PET scans reveal which specific brain regions are activated by a given task
  18. 18. PET scans reveal which specific brain regions are activated by a given task Sight Sound Touch Speech
  19. 19. PET scans reveal which specific brain regions are activated by a given task Sight Sound Touch Speech
  20. 20. PET scans reveal which specific brain regions are activated by a given task Sight Sound Touch Speech
  21. 21. PET scans reveal which specific brain regions are activated by a given task Sight Sound Touch Speech
  22. 22. WHERE’S THE MIND? Two schools of thought: Dualism – the mind and body (or brain) are separate. e.g., Plato “father of western dualism” e.g., René Descartes Monism – the mind is the result of brain functioning & follows physical laws e.g., Leonardo da Vinci (1452-1519) stated “mind is a product of the brain” e.g., most modern brain scientists
  23. 23. Physiological Approaches to Consciousness • Consciousness can be altered by changes in brain chemistry and thus we may hypothesize that it is a physiological function, just like behavior • Consciousness and ability to communicate seem to go hand in hand • Verbal communication allows us to send and receive messages from other people as well as send and receive our own messages (and thus think and be aware of our own existence)
  24. 24. Physiological Approach to Consciousness <ul><li>Blindsight – ability of person who cannot see objects in their blind field to accurately reach for them while remaining “unconscious” of perceiving them (e.g., stroke resulting in damage to the visual cortex) </li></ul><ul><li>Split Brain operation – surgical cutting of the corpus callosum which connects the left and right hemispheres (to ameliorate the severity of epilepsy) </li></ul><ul><li>Unilateral Neglect – failure to notice things located to a person’s left (e.g., stroke resulting in damage to the right parietal cortex) </li></ul>Consciousness is not a general property of all parts of the brain
  25. 25. An explanation of the blindsight phenomenon
  26. 26. MRIs of human brain showing corpus callosum (cc) corpus callosum
  27. 27. Identification of an object by smell in a split-brain patient
  28. 28. Identification of an object by sight in a split-brain patient
  29. 29. Angular Gyrus Activity and the Out of Body Experience
  30. 30. END – Lecture 01
  31. 31. ORGANIZATION OF THE NERVOUS SYSTEM • CNS vs. PNS THE CENTRAL NERVOUS SYSTEM I • Meninges, Ventricles, and Cerebrospinal Fluid • The Spinal Cord • Anatomical Coordinates PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 02 (September 13, 2010)
  32. 32. Organization of the Nervous System <ul><li>Central Nervous System or CNS </li></ul><ul><ul><ul><li>• brain </li></ul></ul></ul><ul><ul><ul><li>• spinal cord </li></ul></ul></ul><ul><li>Peripheral Nervous System or PNS </li></ul><ul><ul><ul><li>• outside the spinal cord </li></ul></ul></ul>
  33. 33. The Meninges Line and Protect the CNS <ul><li>3 Layers: </li></ul><ul><li>dura mater – tough outer layer </li></ul><ul><li>arachnoid layer – middle vascular layer </li></ul><ul><ul><li>• serves to return CSF from base of spinal cord back to brain ( and blood stream via arachnoid villi ) </li></ul></ul><ul><li>pia mater – delicate innermost layer </li></ul>
  34. 34. Ventricles & Flow of CSF • Lateral ventricle (2) • Third ventricle – aqueduct of Sylvius • Fourth ventricle – central canal
  35. 35. Flow of CSF (Choroid Plexus Produces CSF) * * * * * * • CSF flows from choroid plexus (cells that make CSF) • CSF vol ~125 mL, continuously produced with half life ~3 hr • CSF circulates and then returns to blood stream via arachnoid villi or granulations (absorb CSF)
  36. 36. Different Views of the Ventricles & Flow of CSF
  37. 37. CSF Flows Down Spinal Cord via the Central Canal
  38. 39. <ul><li>5 Segments of the Spinal Cord </li></ul><ul><li>Cervical </li></ul><ul><li>Thoracic </li></ul><ul><li>Lumbar </li></ul><ul><li>Sacral </li></ul><ul><li>Coccygeal </li></ul>
  39. 40. Anatomical Planes
  40. 41. Anatomical Planes
  41. 42. Anatomical Planes
  42. 43. Anatomical Directions
  43. 44. END – Lecture 02
  44. 45. <ul><li>THE CENTRAL NERVOUS SYSTEM II </li></ul><ul><li>The Brain </li></ul><ul><ul><li>• Forebrain ( prosencephalon ) </li></ul></ul><ul><ul><ul><li>• Midbrain ( mesencephalon ) </li></ul></ul></ul><ul><ul><ul><li>• Hindbrain ( rhombencephalon ) </li></ul></ul></ul>PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 03 (September 15, 2010)
  45. 46. 3 Major Divisions of the Brain <ul><li>Prosencephalon ( Forebrain ) </li></ul><ul><ul><li>• telencephalon (cerebrum, limbic system, basal ganglia) </li></ul></ul><ul><ul><li>• diencephalon (thalamus, hypothalamus) </li></ul></ul><ul><li>Mesencephalon ( Midbrain ) – smallest of the 3 divisions </li></ul><ul><ul><li>• dorsal portion or tectum (superior & inferior colliculi) </li></ul></ul><ul><ul><li>• tegmentum (red nucleus, periaqueductal gray, substantia nigra) </li></ul></ul><ul><ul><ul><li>• ventral portion (tracts connecting forebrain & hindbrain) </li></ul></ul></ul><ul><li>Rhombencephalon ( Hindbrain ) </li></ul><ul><ul><ul><li>• metencephalon (cerebellum , pons) </li></ul></ul></ul><ul><ul><ul><li>• myelencephalon (medulla) </li></ul></ul></ul>Brain Stem = diencephalon & mesenephalon & rhombencephalon
  46. 47. <ul><li>Prosencephalon ( Forebrain ) – thinking, creating, speaking, </li></ul><ul><li>planning, emotions, etc… ( pretty much all that makes us human ) </li></ul><ul><ul><li>1. telencephalon </li></ul></ul><ul><ul><li>• cerebrum </li></ul></ul><ul><ul><li>• limbic system (hippocampus, amygdala, septum) </li></ul></ul><ul><ul><li>• basal ganglia </li></ul></ul><ul><ul><li>2. diencephalon </li></ul></ul><ul><ul><li>• thalamus </li></ul></ul><ul><ul><li>• hypothalamus </li></ul></ul>
  47. 48. The Cerebrum Central Sulcus separates frontal ( precentral gyrus ) from parietal ( postcentral gyrus ) Sylvian Fissure or Lateral Sulcus separates the temporal lobe from other lobes Sulci are fissures or grooves; Gyri are raised areas or outward bumps The Four Lobes of the Cerebrum
  48. 49. The Major Lobes of the Cerebrum The Cerebrum
  49. 50. <ul><li>Frontal lobes </li></ul><ul><ul><ul><li>• motor cortex , premotor cortex , prefrontal cortex </li></ul></ul></ul><ul><ul><ul><li>• prefrontal cortex – executive functions, including short-term </li></ul></ul></ul><ul><ul><ul><li>memory, decision making, prioritizing behaviors </li></ul></ul></ul><ul><li>Parietal lobes </li></ul><ul><ul><ul><li>• postcentral gyrus, secondary somatosensory cortex </li></ul></ul></ul><ul><ul><ul><li>• somatosensory cortex processes sensory information </li></ul></ul></ul><ul><li>Occipital lobes </li></ul><ul><ul><ul><li>• visual cortex processes visual information </li></ul></ul></ul><ul><li>Temporal lobes </li></ul><ul><ul><ul><li>• auditory cortex, olfactory cortex </li></ul></ul></ul><ul><ul><ul><li>• amygdala and hippocampus (emotions; learning & memory) </li></ul></ul></ul>Lobes of the Cerebrum
  50. 51. <ul><li>The Cerebral Hemispheres are Connected by: </li></ul><ul><li>Corpus Callosum – connects left and right frontal, parietal, occipital </li></ul><ul><li>Anterior Commissure – connects left and right temporal lobes </li></ul><ul><ul><ul><ul><ul><li>(e.g., hippocampus, amygdala) </li></ul></ul></ul></ul></ul>The Cerebrum The Cerebrum contains: Gray Matter (5-7 layers of neurons) and White Matter (axons) (the cerebral Gray matter is also called the cerebral cortex)
  51. 52. Cross Section through the Cerebrum
  52. 53. The Cerebrum Anterior Commissure Note that the line from the label “Cerebral Cortex” at the upper left seems to point to white matter. However, the term Cerebral Cortex is generally used to refer to the Gray Matter.
  53. 54. Diffusion Tensor Imaging of Corpus Callosum Projections Diffusion Tensor Imaging involves a modified MRI magnet. It enables visualization of bundles of axons (the processes that transmit signals from one cell to another)
  54. 55. <ul><li>Prosencephalon ( Forebrain ) – thinking, creating, speaking, </li></ul><ul><li>planning, emotions (pretty much all that makes us human) </li></ul><ul><ul><li>1. telencephalon </li></ul></ul><ul><ul><li>• cerebrum </li></ul></ul><ul><ul><li>• limbic system (hippocampus, amygdala, septum) </li></ul></ul><ul><ul><li>• basal ganglia </li></ul></ul><ul><ul><li>2. diencephalon </li></ul></ul><ul><ul><li>• thalamus </li></ul></ul><ul><ul><li>• hypothalamus </li></ul></ul>
  55. 56. Limbic System – a circuit of structures involved in emotion and memory (Paul MacLean, 1949) <ul><li>Hippocampus </li></ul><ul><ul><ul><li>• sea horse shaped structure in temporal lobes </li></ul></ul></ul><ul><ul><ul><li>• important for forming long-term memories </li></ul></ul></ul><ul><li>Amygdala </li></ul><ul><ul><ul><li>• important for emotions </li></ul></ul></ul><ul><ul><ul><li>• produces fear, aggression </li></ul></ul></ul><ul><ul><ul><li>• Rabies virus attacks the amygdala </li></ul></ul></ul><ul><li>Septum </li></ul><ul><ul><ul><li>• stimulation produces pleasure </li></ul></ul></ul><ul><li>Mamillary Bodies </li></ul><ul><ul><ul><li>• hypothalamic nuclei interconnected with hippocampus </li></ul></ul></ul><ul><ul><ul><li>• important for emotion and memory </li></ul></ul></ul>Other regions also make up what is called the “limbic system”
  56. 57. Schematic of Limbic Structures
  57. 58. Superior View of Limbic Structures Side View of Limbic Structures (without any other brain regions)
  58. 59. <ul><li>Prosencephalon ( Forebrain ) – thinking, creating, speaking, </li></ul><ul><li>planning, emotions (pretty much all that makes us human) </li></ul><ul><ul><li>1. telencephalon </li></ul></ul><ul><ul><li>• cerebrum </li></ul></ul><ul><ul><li>• limbic system (hippocampus, amygdala, septum) </li></ul></ul><ul><ul><li>• basal ganglia </li></ul></ul><ul><ul><li>2. diencephalon </li></ul></ul><ul><ul><li>• thalamus </li></ul></ul><ul><ul><li>• hypothalamus </li></ul></ul>
  59. 60. Basal Ganglia – a cluster of neuronal structures concerned with the production of movement. <ul><li>Putamen and Globus Pallidus </li></ul><ul><ul><ul><li>• egg-shaped structure in each hemisphere </li></ul></ul></ul><ul><li>Caudate </li></ul><ul><ul><ul><li>• tail-shaped structure </li></ul></ul></ul>Basal ganglia structures are implicated in a variety of disorders, including Obsessive-Compulsive Disorder, Parkinson’s disease, and Huntington’s chorea
  60. 61. Location of the Basal Ganglia & Thalamus
  61. 62. <ul><li>Prosencephalon ( Forebrain ) – thinking, creating, speaking, </li></ul><ul><li>planning, emotions (pretty much all that makes us human) </li></ul><ul><ul><li>1. telencephalon </li></ul></ul><ul><ul><li>• cerebrum </li></ul></ul><ul><ul><li>• limbic system (hippocampus, amygdala, septum) </li></ul></ul><ul><ul><li>• basal ganglia </li></ul></ul><ul><ul><li>2. diencephalon </li></ul></ul><ul><ul><li>• thalamus </li></ul></ul><ul><ul><li>• hypothalamus </li></ul></ul>
  62. 63. Diencephalon – forebrain region that surrounds the 3rd ventricle <ul><li>Thalamus </li></ul><ul><ul><ul><li>• a large number of nuclei in each hemisphere </li></ul></ul></ul><ul><ul><ul><li>• look like flattened egg-shaped structures </li></ul></ul></ul><ul><ul><ul><li>• relays information to and from the cerebrum </li></ul></ul></ul><ul><li>Hypothalamus </li></ul><ul><ul><ul><li>• series of nuclei (located below thalamus) </li></ul></ul></ul><ul><ul><ul><li>• controls activity of the pituitary gland </li></ul></ul></ul><ul><ul><ul><li>• important for many regulated behaviors including: </li></ul></ul></ul><ul><ul><ul><li>– eating and drinking </li></ul></ul></ul><ul><ul><ul><li>– sleeping </li></ul></ul></ul><ul><ul><ul><li>– temperature control </li></ul></ul></ul><ul><ul><ul><li>– sexual and emotional </li></ul></ul></ul>
  63. 64. Thalamic Connections with the Cortex
  64. 65. Thalamic Connections using Diffusion Tensor Imaging
  65. 66. Location of the Hypothalamus & Pituitary Gland
  66. 67. Location of the Hypothalamus & Pituitary Gland
  67. 68. 3 Major Divisions of the Brain <ul><li>Prosencephalon ( Forebrain ) </li></ul><ul><ul><li>• telencephalon (cerebrum, limbic system, basal ganglia) </li></ul></ul><ul><ul><li>• diencephalon (thalamus, hypothalamus) </li></ul></ul><ul><li>Mesencephalon ( Midbrain ) – smallest of the 3 divisions </li></ul><ul><ul><li>• dorsal portion or tectum (superior & inferior colliculi) </li></ul></ul><ul><ul><li>• tegmentum (red nucleus, periaqueductal gray, substantia nigra) </li></ul></ul><ul><ul><ul><li>• ventral portion (tracts connecting forebrain & hindbrain) </li></ul></ul></ul><ul><li>Rhombencephalon ( Hindbrain ) </li></ul><ul><ul><ul><li>• metencephalon (cerebellum, pons) </li></ul></ul></ul><ul><ul><ul><li>• myelencephalon (medulla) </li></ul></ul></ul>Brain Stem = diencephalon & mesenephalon & rhombencephalon
  68. 69. <ul><li>Mesencephalon ( Midbrain ) – also contains the reticular formation which runs from hindbrain to forebrain </li></ul><ul><ul><li>reticular formation </li></ul></ul><ul><ul><li> • consists of many nuclei & a diffuse network of interconnected neurons (reticular = little net) </li></ul></ul><ul><ul><li> • important in arousal (alerts forebrain to important stimuli) </li></ul></ul><ul><ul><li> • damage results in a coma </li></ul></ul>
  69. 70. 3 Major Divisions of the Brain <ul><li>Prosencephalon ( Forebrain ) </li></ul><ul><ul><li>• telencephalon (cerebrum, limbic system, basal ganglia) </li></ul></ul><ul><ul><li>• diencephalon (thalamus, hypothalamus) </li></ul></ul><ul><li>Mesencephalon ( Midbrain ) – smallest of the 3 divisions </li></ul><ul><ul><li>• dorsal portion or tectum (superior & inferior colliculi) </li></ul></ul><ul><ul><li>• tegmentum (red nucleus, periaqueductal gray, substantia nigra) </li></ul></ul><ul><ul><ul><li>• ventral portion (tracts connecting forebrain & hindbrain) </li></ul></ul></ul><ul><li>Rhombencephalon ( Hindbrain ) </li></ul><ul><ul><ul><li>• metencephalon (cerebellum, pons) </li></ul></ul></ul><ul><ul><ul><li>• myelencephalon (medulla) </li></ul></ul></ul>Brain Stem = diencephalon & mesenephalon & rhombencephalon
  70. 71. <ul><li>Rhombencephalon ( Hindbrain ) – immediately superior to spinal cord </li></ul><ul><ul><li>1. Cerebellum </li></ul></ul><ul><ul><li>• located dorsal to both medulla and pons </li></ul></ul><ul><ul><li>• contains a cortex and underlying white matter </li></ul></ul><ul><ul><li>• coordination of movement </li></ul></ul><ul><ul><li>• alcohol impairs cerebellar function </li></ul></ul><ul><ul><li>2. Pons </li></ul></ul><ul><ul><li>• located superior to the medulla </li></ul></ul><ul><ul><li>• composed mostly of white matter tracts </li></ul></ul><ul><ul><li>• serves as a bridge between cerebral cortex and cerebellum </li></ul></ul><ul><ul><li>3. Medulla </li></ul></ul><ul><ul><li>• located just superior to spinal cord </li></ul></ul><ul><ul><li>• ascending & descending cortical tracts cross over from left to right </li></ul></ul><ul><ul><li>• controls many life-support functions ( breathing, HR, coughing, vomiting) </li></ul></ul>Metencephalon (cerebellum & pons) ; Myelencephalon (medulla)
  71. 72. Midsagittal view of Forebrain, Midbrain, & Hindbrain
  72. 73. Parts of the Forebrain, Midbrain, & Hindbrain
  73. 74. Human Brainstem
  74. 75. END – Lecture 03
  75. 76. <ul><li>DIVISIONS OF THE PERIPHERAL NERVOUS SYSTEM </li></ul><ul><li>Somatic vs. Autonomic </li></ul><ul><li>Sympathetic vs. Parasympathetic </li></ul><ul><li>Peripheral Nerves </li></ul><ul><ul><li>• Cranial nerves </li></ul></ul><ul><ul><li>• Spinal nerves </li></ul></ul><ul><li>Organization of the PNS </li></ul>PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 04 (September 20, 2010)
  76. 77. Divisions of the Peripheral Nervous System <ul><li>Somatic Nervous System </li></ul><ul><ul><ul><li>• controls skeletal muscles </li></ul></ul></ul><ul><ul><ul><li>• under voluntary control </li></ul></ul></ul><ul><li>Autonomic Nervous System </li></ul><ul><ul><ul><li>• controls smooth and cardiac muscle </li></ul></ul></ul><ul><ul><ul><li>• NOT under voluntary control </li></ul></ul></ul>
  77. 78. Divisions of the Autonomic Nervous System <ul><li>Sympathetic Nervous System </li></ul><ul><ul><ul><li>• fight-or-flight system </li></ul></ul></ul><ul><ul><ul><li>• dilates pupils </li></ul></ul></ul><ul><ul><ul><li>• accelerates heart rate </li></ul></ul></ul><ul><ul><ul><li>• relaxes bronchi </li></ul></ul></ul><ul><ul><ul><li>• increases blood flow to muscles </li></ul></ul></ul><ul><ul><ul><li>• decreases blood flow to stomach & internal organs </li></ul></ul></ul><ul><li>Parasympathetic Nervous System </li></ul><ul><ul><ul><li>• energy conservation system </li></ul></ul></ul><ul><ul><ul><li>• constricts pupils </li></ul></ul></ul><ul><ul><ul><li>• slows heart rate </li></ul></ul></ul><ul><ul><ul><li>• constricts bronchi </li></ul></ul></ul><ul><ul><ul><li>• increases blood flow to stomach & internal organs </li></ul></ul></ul>
  78. 79. Divisions of the Autonomic Nervous System <ul><li>Eyes </li></ul><ul><li>Lungs </li></ul><ul><li>Heart </li></ul><ul><li>Stomach, Intestines </li></ul><ul><li>Blood vessels of internal organs </li></ul>
  79. 80. PNS Transmits Information to the Body via 43 Pairs of Nerves • 12 pairs of CRANIAL NERVES – enter & exit the brain through holes in skull • 31 pairs of SPINAL NERVES – enter & exit the spinal cord between vertebrae
  80. 81. CRANIAL NERVES (12 pairs, CNs I through XII) • enter & exit the brain through holes ( foramena ) in skull • permit direct communication between brain & PNS • allow for sensory input from head, neck, upper abdomen • allow for motor output from brain to skeletal muscles in head and neck • allow for parasympathetic output to smooth muscles in head, neck, and upper abdomen • CNs I & II go to forebrain (prosencephalon) • CNs III & IV arise from midbrain (mesencephalon) • CNs V–XII enter & exit the hindbrain (rhombencephalon)
  81. 82. CRANIAL NERVES (12 pairs) 3 of the cranial nerves serve sensory functions only: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III • CN IV • CN V • CN VI • CN VII • CN VIII (auditory nerve) – sensory ; hearing • CN IX • CN X • CN XI • CN XII
  82. 83. Red is motor Blue is Sensory
  83. 84. CRANIAL NERVES (12 pairs) 3 of the cranial nerves control eye movement: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V • CN VI (abducens nerve) – motor, eye movement • CN VII • CN VIII (auditory nerve) – sensory ; hearing • CN IX • CN X • CN XI • CN XII
  84. 85. Red is motor Blue is Sensory
  85. 86. CRANIAL NERVES (12 pairs) 2 of the cranial nerves control facial muscles: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory ; hearing • CN IX • CN X • CN XI • CN XII
  86. 87. Red is motor Blue is Sensory
  87. 88. CRANIAL NERVES (12 pairs) 2 of the cranial nerves control throat and tongue muscles: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory ; hearing • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste • CN X • CN XI • CN XII (hypoglossal nerve) – motor, tongue movements
  88. 89. Red is motor Blue is Sensory
  89. 90. CRANIAL NERVES (12 pairs) 1 cranial nerve wanders to the head, neck, & upper abdomen: • CN I (olfactory nerve) – sensory ; smell • CN II (optic nerve) – sensory ; sight • CN III (oculomotor nerve) – motor, eye movement • CN IV (trochlear nerve) – motor, eye movement • CN V (trigeminal nerve) – motor, chewing; sensory, face & head • CN VI (abducens nerve) – motor, eye movement • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face • CN VIII (auditory nerve) – sensory ; hearing • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste • CN X (vagus nerve) – motor, smooth muscles of neck, chest & upper abdomen; sensory, taste, organs of chest & upper abdomen • CN XI • CN XII (hypoglossal nerve) – motor, tongue movements
  90. 91. Red is motor Blue is Sensory
  91. 92. CRANIAL NERVES (12 pairs) 1 cranial nerve is motor only & innervates neck muscles: • CN I (olfactory nerve) – sensory ; smell (S) • CN II (optic nerve) – sensory ; sight (S) • CN III (oculomotor nerve) – motor, eye movement (M) • CN IV (trochlear nerve) – motor, eye movement (M) • CN V (trigeminal nerve) – motor, chewing; sensory, face & head (B) • CN VI (abducens nerve) – motor, eye movement (M) • CN VII (facial nerve) – motor, facial muscles; sensory, taste & face (B) • CN VIII (auditory nerve) – sensory ; hearing (S) • CN IX (glossopharyngeal) – motor, throat & larynx; sensory, taste (B) • CN X (vagus nerve) – motor, smooth muscles of thoracic & upper abdomen; sensory, taste, organs of chest & upper abdomen (B) • CN XI (accessory nerve) – motor only, skeletal muscles of neck (M) • CN XII (hypoglossal nerve) – motor, tongue movements (M) Mnemonic: S ome S ay M oney M atters B ut M y B rother S ays B ig B rains M atter M ore ( S = sensory; M = motor; B = both)
  92. 93. Red is motor Blue is Sensory
  93. 94. The Cranial Nerves & Their Functions Bell’s Palsy – facial paralysis caused by an infection of the facial nerve ( CN VII ). Results in paralysis on that side of face (not usually permanent).
  94. 95. PNS Transmits Information to the Body via 43 Pairs of Nerves • 12 pairs of CRANIAL NERVES – enter & exit the brain through holes in skull • 31 pairs of SPINAL NERVES – enter & exit the spinal cord between vertebrae
  95. 96. Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra
  96. 97. Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra
  97. 98. Spinal Nerves Exit the Spinal Cord Between Adjacent Vertebra
  98. 99. Cross Section of Spinal Cord <ul><li>Sensory is Dorsal (signals enter) </li></ul><ul><li>Motor is Ventral (signals exit the cord) </li></ul><ul><li>(Bell-Magendie law) </li></ul>
  99. 100. SPINAL NERVES (31 pairs) • enter & exit the spinal cord between vertebrae • 8 pairs arise from Cervical region ( C1–C8 ) • 12 pairs arise from Thoracic region ( T1–T12 ) • 5 pairs arise from the Lumbar region ( L1–L5 ) • 5 pairs arise from the Sacral region ( S1–S5 ) • 1 pair arises from the Coccygeal region <ul><li>For a given region, lower numbers are superior (or higher) along the cord. </li></ul><ul><li>Thus, C1 is superior to C2, etc… </li></ul><ul><li>(2) In spinal cord damage, the higher the lesion on the spinal cord </li></ul><ul><li>( e.g., C is higher than T or L ), the more severe the injury. </li></ul>
  100. 101. <ul><li>5 Segments of the Spinal Cord </li></ul><ul><li>Cervical </li></ul><ul><li>Thoracic </li></ul><ul><li>Lumbar </li></ul><ul><li>Sacral </li></ul><ul><li>Coccygeal </li></ul>
  101. 102. Dermatome Map • The body area innervated by one spinal nerve Q: Why do you not see C1 on the dermatome map to the right?
  102. 103. Sacral–Parasympathetic (anus, genitals, & bladder) Cranial–Parasympathetic (organs, vessels, and muscles, etc…) Thoracic & Lumbar – Sympathetic (organs, vessels, muscles, anus, genitals, bladder, etc…) Distribution of the Autonomic Nervous System
  103. 104. • thoracolumbar • craniosacral Distribution of the Autonomic Nervous System
  104. 105. END – Lecture 04
  105. 106. <ul><li>NEURONS AND GLIAL CELLS </li></ul><ul><li>Structure of Neurons </li></ul><ul><ul><ul><li>• Soma </li></ul></ul></ul><ul><ul><ul><li>• Dendrites </li></ul></ul></ul><ul><ul><ul><li>• Axons </li></ul></ul></ul><ul><li>Classifying Neurons </li></ul><ul><ul><ul><li>• Anatomical </li></ul></ul></ul><ul><ul><ul><li>• Functional </li></ul></ul></ul><ul><li>Glial Cells </li></ul><ul><li>• Types of Glia </li></ul><ul><li>• Role in Axon Myelination </li></ul>PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 05 (September 22, 2010)
  106. 107. The Nervous System Two Types of Cells: 1. Neurons – cells of the nervous system 2. Glia – support cells Historically: • 1840 – Schleiden & Schwann proposed cells were basic units of tissue • However, scientists thought that nervous tissue was not made of cells 1860s Golgi – Silver impregnation 1892 Cajal – Neuron doctrine 1906 Golgi & Cajal were awarded the Nobel Prize Camillo Golgi (1843-1926) Ramón y Cajal (1852-1934)
  107. 108. 3 Parts of a Neuron <ul><li>Soma or cell body (contains nucleus, etc…) </li></ul><ul><li>Dendrite (transmits signals toward soma) </li></ul><ul><ul><ul><li>• some cells have few dendrites </li></ul></ul></ul><ul><ul><ul><li>• some cells have many dendrites </li></ul></ul></ul><ul><li>Axon (transmits signals from soma – output) </li></ul><ul><ul><ul><li>• all cells have one axon </li></ul></ul></ul><ul><ul><ul><li>• axon can branch many times </li></ul></ul></ul>
  108. 109. Example of a Motor Neuron
  109. 110. Parts of a Neuron
  110. 111. Information Flow Between and Within Neurons 1. Signal enters dendrite or soma 2. Signal travels from soma to axon 3. Signal travels down axon 4. Signal leaves axon and enters dendrite or soma
  111. 112. Divergence (e.g., sensory) Convergence (e.g., motor) Information Flow Between Neurons
  112. 113. Basic Subcellular Components of Mammalian cells (similar for neurons)
  113. 114. Structure of Neurons
  114. 115. Major Organelles <ul><li>Nucleus – contains DNA. Gene expression occurs by transcription of DNA into RNA, which is exported out of the cell and used as a template to make proteins. </li></ul><ul><li>Endoplasmic reticulum – membranous organelle that makes lipids and proteins. There are two varieties observed in cells: </li></ul><ul><ul><ul><li>Rough ER (studded with ribosomes) - used to make secreted and membrane-bound proteins. </li></ul></ul></ul><ul><ul><ul><li>Smooth ER (without ribosomes) - used to make lipids. </li></ul></ul></ul><ul><li>Golgi apparatus – membranous structure that modifies and stores the proteins and lipids made in the endoplasmic reticulum. </li></ul><ul><li>Mitochondria – fuel powerhouse of the cell. Produces ATP (adenosine triphosphate), which is used as an energy source for chemical reactions. </li></ul><ul><li>Cell membrane – phospholipid bilayer that surrounds the cell. In neurons, it contains proteins called ion channels that are selectively permeable to various salts or ions (e.g., calcium, sodium, chloride, potassium, etc…). </li></ul>
  115. 116. Cell Nucleus and Protein Synthesis Chromosomes contain genetic information, 23 pairs – 22 pairs are autosomal – the final pair are sex chromosomes (XX or XY) – the 23 pair of chromosomes contain ~20,000 to 25,000 genes Genome refers to the sum total of all the genes; same in every cell Nucleic acids are specialized compounds that contain a nitrogenous base, a sugar, and a phosphoric acid • Deoxyribonucleic acid (DNA ) encodes the genetic material of a cell – found in the nucleus (and in mitochondria) • Contains 4 nitrogen bases: Adenine, Guanine, Cytosine, Thymine • Nucleoside is nitrogen base + sugar (2-deoxyribose) • Nucleotide is base-sugar + phosphoric acid • Ribonucleic acid (RNA ) serves as blueprint for proteins – generally found in the cytoplasm as mRNA and ribosomes – also contain 4 nitrogen bases: Adenine, Guanine, Cytosine, Uracil – triplet base pairs encode specific amino acids (e.g., UGG = tryptophan ) – ribosomes read mRNA and add appropriate amino acids to make protein
  116. 117. Structure of Neurons
  117. 118. Examples of Genetic Alterations that affect Brain Function Fragile-X Syndrome – normally the X chromosome (FMR1 gene has a CGG triad repeated 10-30 times ) – in fragile-X, the CGG triad is repeated hundreds of times – produces mental retardation (disrupted synaptic connections) Mental retardation also results from untreated phenylketonuria (PKU) which is linked to an altered gene on chromosome 12 ( lack of phenylalanine hydroxylase ) Down Syndrome – Results from a trisomy of chromosome 21 (3 copies instead of 2) – leads to faulty brain development and cognitive impairments as well as other skeletal and soft tissue abnormalities
  118. 119. Classifying Neurons 1. Based on anatomical or morphological features (Ramón y Cajal) – unipolar (or monopolar) neuron – bipolar neuron – pseudo-unipolar neuron – multipolar neuron 2. Based on functionality (often used to describe neurons in the spinal cord) – motor neuron – sensory neuron – interneuron
  119. 120. Anatomical Classifications
  120. 121. Example of a Sensory Neuron Note: functionally, this pseudo-unipolar cell contains one axon (on the left) and a sensory process on the right, however this process is functionally an axon (it reliably transmits electrical spikes from the skin to the CNS). Only the sensory endings are technically dendrites. Warning: some people (including your text) refer to pseudo-unipolar cells as unipolar cells, I maintain a separate classification between these, however both are exclusively sensory neurons .
  121. 122. Functional Classifications <ul><li>Motor neuron </li></ul><ul><li>Sensory neuron </li></ul><ul><li>Interneuron </li></ul>
  122. 123. Functional Classifications <ul><li>Motor neuron </li></ul><ul><li>Sensory neuron </li></ul><ul><li>Interneuron </li></ul>Bell-Magendie law – sensory enters dorsal, motor exits ventral Note:
  123. 124. Glial Cells <ul><li>“ glue ” that holds the nervous system together </li></ul><ul><li>There are 10 times as many glial cells as neurons </li></ul><ul><ul><li>– about 100 billion neurons (100,000,000,000) </li></ul></ul><ul><ul><li>– thus, there are at least 1 trillion glia (1,000,000,000,000) </li></ul></ul><ul><li>Many are much smaller than neurons </li></ul>
  124. 125. Roles of Glial Cells in the Nervous System <ul><li>Provide nourishment for neurons </li></ul><ul><ul><ul><li>Astrocytes surround blood vessels & obtain nutrients </li></ul></ul></ul><ul><li>Remove waste and dead neurons </li></ul><ul><ul><ul><li>Astrocytes and Microglia (also function as macrophages ) </li></ul></ul></ul><ul><li>Form scar tissue in the nervous system </li></ul><ul><ul><ul><li>Astrocytes migrate into empty space </li></ul></ul></ul><ul><ul><ul><li>Gliosis is the accumulation of glia in brain tissue </li></ul></ul></ul><ul><li>Direct development of the nervous system </li></ul><ul><ul><ul><li>Radial glia direct neuronal migration </li></ul></ul></ul><ul><li>Provide axonal myelination </li></ul><ul><ul><ul><li>Schwann cells myelinate axons in the PNS </li></ul></ul></ul><ul><ul><ul><li>Oligodendrocytes myelinate axons in the CNS </li></ul></ul></ul><ul><li>Contribute to blood-brain barrier (fat-soluble enter easily) </li></ul><ul><ul><ul><li>Astrocytes form tight junctions with capillary endothelium </li></ul></ul></ul>
  125. 126. Glial Cells – Astrocytes
  126. 127. Myelination of Axons Schwann Cells (PNS) Oligodendrocytes (CNS) Value of myelination: 1. Speeds axonal transmission (action potential jumps from node of Ranvier to node of Ranvier instead of traveling down entire axon (Saltatory Conduction) 2. Assist in axon regeneration (Schwann cells only)
  127. 128. Electron Micrograph of a Schwann Cell Schwann Cells – myelinate only one segment of one axon
  128. 129. Comparison of Oligodendrocytes and Schwann Cells
  129. 130. Oligodendrocytes myelinate multiple segments of multiple axons
  130. 131. Blood-Brain Barrier
  131. 132. Blood-Brain Barrier
  132. 133. END – Lecture 05
  133. 134. Parts of a Cell Slides <ul><li>These slides contain background information the majority of which you are expected to know prior to taking physiological psychology. </li></ul><ul><li>If this material is not familiar to you, please read pages 30-36 of the Carlson text [if you don’t have the Carlson text, similar material is contained in virtually any physiological psychology text (usually in chapter 2 or 3) </li></ul>
  134. 135. Structure of Neurons
  135. 136. Major Organelles <ul><li>Nucleus – contains DNA. Gene expression occurs by transcription of DNA into RNA, which is exported out of the cell and used as a template to make proteins. </li></ul><ul><li>Endoplasmic reticulum – membranous organelle that makes lipids and proteins. There are two varieties observed in cells: </li></ul><ul><ul><ul><li>Rough ER (studded with ribosomes) - used to make secreted and membrane-bound proteins. </li></ul></ul></ul><ul><ul><ul><li>Smooth ER (without ribosomes) - used to make lipids. </li></ul></ul></ul><ul><li>Golgi apparatus – membranous structure that modifies and stores the proteins and lipids made in the endoplasmic reticulum. </li></ul><ul><li>Mitochondria – fuel powerhouse of the cell. Produces ATP (adenosine triphosphate), which is used as an energy source for chemical reactions. </li></ul><ul><li>Cell membrane – phospholipid bilayer that surrounds the cell. In neurons, it contains proteins called ion channels that are selectively permeable to various salts or ions (e.g., calcium, sodium, chloride, potassium, etc…). </li></ul>
  136. 137. Cell Nucleus and Protein Synthesis Chromosomes contain genetic information, 23 pairs – 22 pairs are autosomal – the final pair are sex chromosomes (XX or XY) – the 23 pair of chromosomes contain ~20,000 to 25,000 genes Genome refers to the sum total of all the genes; same in every cell Nucleic acids are specialized compounds that contain a nitrogenous base, a sugar, and a phosphoric acid • Deoxyribonucleic acid (DNA ) encodes the genetic material of a cell – found in the nucleus (and in mitochondria) • Contains 4 nitrogen bases: Adenine, Guanine, Cytosine, Thymine • Nucleoside is nitrogen base + sugar (2-deoxyribose) • Nucleotide is base-sugar + phosphoric acid • Ribonucleic acid (RNA ) serves as blueprint for proteins – generally found in the cytoplasm as mRNA and ribosomes – also contain 4 nitrogen bases: Adenine, Guanine, Cytosine, Uracil – triplet base pairs encode specific amino acids (e.g., UGG = tryptophan ) – ribosomes read mRNA and add appropriate amino acids to make protein
  137. 138. Structure of Neurons
  138. 139. Examples of Genetic Alterations that affect Brain Function Fragile-X Syndrome – normally the X chromosome (FMR1 gene has a CGG triad repeated 10-30 times ) – in fragile-X, the CGG triad is repeated hundreds of times – produces mental retardation (disrupted synaptic connections) Mental retardation also results from untreated phenylketonuria (PKU) which is linked to an altered gene on chromosome 12 ( lack of phenylalanine hydroxylase ) Down Syndrome – Results from a trisomy of chromosome 21 (3 copies instead of 2) – leads to faulty brain development and cognitive impairments as well as other skeletal and soft tissue abnormalities
  139. 140. <ul><li>How Do Neurons Communicate? </li></ul><ul><ul><ul><li>• chemical & electrical transmission </li></ul></ul></ul><ul><li>Chemical Synapse </li></ul><ul><ul><li>• components of a synapse </li></ul></ul><ul><ul><li>• types of synapses </li></ul></ul><ul><ul><li>• neurotransmitters </li></ul></ul><ul><li>Neuronal Membrane Properties </li></ul><ul><ul><li>• neuronal cell membrane </li></ul></ul><ul><ul><li>• membrane potential </li></ul></ul><ul><ul><li>• distribution of ions </li></ul></ul><ul><ul><li>• ion channels </li></ul></ul><ul><ul><li>• depolarization & hyperpolarization </li></ul></ul><ul><ul><li>• action potential </li></ul></ul><ul><li>Signal Integration </li></ul><ul><ul><li>• summation </li></ul></ul><ul><ul><li>• excitation and inhibition </li></ul></ul>PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 06 (September 27, 2010)
  140. 141. How Do Neurons Communicate? <ul><li>Chemical Transmission </li></ul><ul><ul><li>• Releasing chemicals onto another neuron </li></ul></ul><ul><li>Electrical Transmission </li></ul><ul><ul><ul><li>• Gap Junctions ( electrical coupling between cells) </li></ul></ul></ul><ul><ul><ul><li>• Propagating signals within a neuron </li></ul></ul></ul><ul><ul><ul><li>a) membrane depolarization or hyperpolarization </li></ul></ul></ul><ul><ul><ul><li>b) action potential propagation </li></ul></ul></ul>
  141. 142. Synapse – the junction between two connected neurons (Sherrington, 1906) Synapse is composed of: 1. presynaptic membrane 2. synaptic cleft (<300 Å or 30 nm) 3. postsynaptic membrane Chemical Synapse During an impulse, or action potential, neurotransmitter vesicles fuse with the presynaptic membrane and release neurotransmitters into the synaptic cleft. They then diffuse across the cleft and bind to receptors on the postsynaptic neuronal membrane.
  142. 143. Electron Micrograph of an axodendritic synapse
  143. 144. EM of axodendritic synapse Mag: 280,000 X
  144. 145. Types of Synapses in the Nervous System <ul><li>Axodendritic </li></ul><ul><ul><li>– onto dendrites (a) </li></ul></ul><ul><ul><li>– onto spines (b) </li></ul></ul><ul><li>Axosomatic (c) </li></ul><ul><li>Axoaxonic (d) </li></ul><ul><li>Dendrodendritic </li></ul><ul><li>Neuromuscular junction – axon synapses onto muscle cell </li></ul>
  145. 146. How Do Neurons Communicate? <ul><li>Chemical Transmission </li></ul><ul><ul><li>• Releasing chemicals onto another neuron </li></ul></ul><ul><li>Electrical Transmission </li></ul><ul><ul><ul><li>• Gap Junctions ( electrical coupling between cells) </li></ul></ul></ul><ul><ul><ul><li>• Propagating signals within a neuron </li></ul></ul></ul><ul><ul><ul><li>a) membrane depolarization or hyperpolarization </li></ul></ul></ul><ul><ul><ul><li>b) action potential propagation </li></ul></ul></ul>
  146. 147. Glial Cells and Neurons can communicate via Gap Junctions Gap junctions – enable electrical coupling between neurons and/or glial cells
  147. 148. Resting Membrane Potential (RMP) • Neurons are bathed in a salt solution (the salts dissociate into ions) • Ions are positive (cations) or negative (anions); e.g., NaCl dissociates into Na + & Cl - • Inside cell is more negative • Outside cell is more positive • cell membrane restricts ion movement • RMP is usually ~ -70 mV
  148. 150. Recording Neuronal Activity Much of what we know about the ionic basis of membrane potential and the action potential was learned using the Squid Giant Axon preparation.
  149. 151. Recording Neuronal Activity
  150. 152. Neuronal Cell Membrane is a Phospholipid Bilayer with Ion Channels Ions (salts) cannot simply diffuse across the cell membrane (they must go through channels) Hydrophilic (attracted to water) & Hydrophobic (repelled from water)
  151. 153. High Na + and Cl - outside (low inside) High K + inside (low outside) Distribution of Ions Across the Neuronal Membrane at Rest
  152. 154. What is the Equilibrium or Reversal Potential of an Ion?
  153. 155. Distribution of Ions Across the Neuronal Membrane at Rest 2 forces at work: chemical and electrical gradients
  154. 156. At Rest During Depolarization • Neuron’s RMP is negative at rest • During depolarization, Na + rushes into cell, making inside more positive • If depolarization is strong enough to fire an Action Potential, the inside will become much more positive than the outside Membrane Potential
  155. 157. • Small inputs are subthreshold (e.g., 1, 2, 3) • If input is large enough, threshold is reached. • At threshold, an Action Potential is initiated (e.g., 4) Relevant Concepts: • All-or-none law • absolute refractory period • relative refractory period The Action Potential
  156. 158. Summary of Ion Channel Activity During an Action Potential
  157. 159. Summary of Ion Flow During an Action Potential <ul><li>Na + influx </li></ul><ul><li>K + efflux </li></ul><ul><li>Overshoot </li></ul>
  158. 160. Conduction of the Action Potential
  159. 161. Movement of an Action Potential down an Unmyelinated Axon
  160. 162. Action Potential Propagation <ul><li>Na + influx </li></ul><ul><li>K + efflux </li></ul><ul><li>Spread of depolarization under the membrane </li></ul><ul><li>Na + influx … </li></ul>
  161. 163. Saltatory Conduction – conserves energy; increases conduction speed (up to 120 m/s or 432 km/hr) Myelination
  162. 164. Saltatory Conduction IMPORTANT CONCEPTS: • Distribution of Na + & K + channels • Spread of electrical charge
  163. 165. Action Potential Propagation THOUGHT QUESTION: Is it better to have a previously myelinated axon become demyelinated or is it better to have an axon that was never myelinated in the first place? Or do they function the same?
  164. 166. The Na-K Pump ( 3 Na + : 2K + ) also called the Na-K ATPase Summary of Action Potential Events 1. During AP, Na + enters 2. After AP begins, K + exits 3. Cell must restore Na + & K + ! Na-K ATPase restores ion balance 1. 3 Na + ions are pumped out 2. 2 K + ions are pumped in
  165. 167. Coding of Stimulus Strength
  166. 168. 1. Temporal summation 2. Spatial summation How does a neuron integrate or add up inputs it receives?
  167. 169. Temporal and Spatial summation
  168. 170. Temporal and Spatial summation
  169. 171. END – Lecture 06
  170. 172. PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 07 (September 29, 2010) <ul><li>Ion Channels </li></ul><ul><ul><ul><li>• ligand-gated </li></ul></ul></ul><ul><ul><ul><li>• voltage-gated </li></ul></ul></ul><ul><ul><ul><li>• ion-gated </li></ul></ul></ul><ul><ul><ul><li>• non-gated </li></ul></ul></ul><ul><li>Ion Channels and Action Potentials </li></ul><ul><li>Neurotransmitter Release at the Terminal Button </li></ul><ul><li>Presynaptic and Postsynaptic Inhibition </li></ul><ul><li>Postsynaptic and Presynaptic Receptors </li></ul><ul><ul><li>• ligand-gated Receptors </li></ul></ul><ul><ul><li>• G-protein linked Receptors </li></ul></ul><ul><li>Drug Actions on Neurotransmission </li></ul>
  171. 173. Four General Classes of Ion Channels
  172. 174. Movement of Sodium Ions with Channel Opening
  173. 175. Basic Steps involved in Transmitter Release
  174. 176. Before the action potential arrives, the postsynaptic ligand-gated channels are closed After the action potential arrives, neurotransmitter is released, binds and causes postsynaptic ligand-gated channels to open Ligand-Gated Ion Channel A B
  175. 177. Schematic of Synaptic Vesicle Release
  176. 178. Steps Involved in Neurotransmitter Release
  177. 179. Neurotransmitter Release & Reuptake
  178. 180. EM of Synaptic Vesicle Release
  179. 181. Summary of Steps Involved in Neurotransmitter Release <ul><li>Action Potential Arrives at axon terminal (Na + influx) </li></ul><ul><li>Neurotransmitter vesicle docks at release site </li></ul><ul><li>The Na + influx causes depolarization which causes voltage-gated Ca 2+ channels to open </li></ul><ul><li>The Ca 2+ influx causes fusion pore to open and vesicle membrane to fuse with axonal presynaptic cell membrane </li></ul><ul><li>Incorporation of vesicle with presynaptic membrane occurs as neurotransmitter is released </li></ul><ul><li>Vesicle membrane gets added to axon terminal cell membrane </li></ul>
  180. 182. Membrane Recycling is Essential <ul><li>Synaptic vesicle fusion </li></ul><ul><li>Pinocytosis of membrane </li></ul><ul><li>Cisterna </li></ul>
  181. 183. <ul><li>Concentration gradient of Na + (more out than in) means that Na + ions flow INTO the cell (and influx of positive charge is depolarization ); same for Ca 2+ ions. </li></ul><ul><li>Result is EPSP (excitatory postsynaptic potential) </li></ul><ul><li>2. Concentration gradient of K + (more in than out) means that K + ions flow OUT of the cell (and an efflux of positive charge is hyperpolarization ) . </li></ul><ul><li>Result is IPSP (inhibitory postsynaptic potential) </li></ul><ul><li>Concentration gradient of Cl - (more out than in) means that Cl - ions flow INTO the cell (and an influx of negative charge is hyperpolarization ) . </li></ul><ul><li>Result is IPSP (inhibitory postsynaptic potential) </li></ul>Why do certain ions/gradients produce EPSPs as opposed to IPSPs?
  182. 184. Movement of Major Ions (EPSPs vs IPSPs)
  183. 185. Postsynaptic and Presynaptic Inhibition Simple Rule of Thumb (each causes hyperpolarization of the membrane): Postsynaptic inhibition decreases a neuron’s responsiveness to inputs (acts at inputs) Presynaptic inhibition decreases a neuron’s ability to release transmitter (acts at output)
  184. 186. Balance between Excitation and Inhibition
  185. 187. 2 Types of Ligand-Gated Receptors <ul><li>Ionotropic Receptors – direct link to ion channel </li></ul><ul><li>Metabotropic Receptors – indirectly linked to ion channel </li></ul>
  186. 188. IONOTROPIC RECEPTORS (e.g., nicotinic AChRs)
  187. 189. <ul><li>Neurotransmitter binds </li></ul><ul><li>G-protein activated </li></ul><ul><li>Adenylate cyclase activated </li></ul><ul><ul><ul><li>– converts ATP into cAMP </li></ul></ul></ul><ul><li>cAMP is a second messenger </li></ul><ul><li>cAMP has numerous effects </li></ul><ul><ul><li>– e.g., activates kinases which can alter the excitability of different ion channels </li></ul></ul>METABOTROPIC RECEPTORS (e.g., muscarinic AChRs)
  188. 190. METABOTROPIC RECEPTORS Effects of Second Messenger Cascades, such as those through metabotropic G-protein-linked receptors, last longer than those through ionotropic ligand-gated receptors.
  189. 191. Agonists and Antagonists • Agonist activates the receptor • Antagonist blocks the receptor
  190. 192. Two Common Types of Agonists and Antagonists DIRECT INDIRECT Competes for same site as neurotransmitter ( competitive ) Does NOT compete for same site as neurotransmitter ( noncompetitive )
  191. 193. FIVE WAYS IN WHICH DRUGS CAN AFFECT SYNAPTIC TRANSMISSION <ul><li>Synthesis of the transmitter ( 1 & 2 ) </li></ul><ul><li>Packaging of the transmitter (loading vesicles; 3 ) </li></ul><ul><li>Shipping of the transmitter (vesicular release; 4 & 5; 8 & 9 ) </li></ul><ul><li>Receiving the transmitter (postsynaptic receptors; 6 & 7 ) </li></ul><ul><li>Recycling or destroying the transmitter (reuptake all of part; 10 & 11 ) </li></ul>Think in terms of a manufacturing plant that needs raw materials to make the product, needs to wrap it for shipping, needs to ship it, needs someone to receive it, and needs to deal with excess product by destroying or recycling the parts.
  192. 194. SUMMARY OF WAYS IN WHICH DRUGS CAN AFFECT SYNAPTIC TRANSMISSION Note: AGO = agonist ( blue Box ); ANT = antagonist ( red Box )
  193. 195. END – Lecture 07
  194. 196. PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 08 (October 04, 2010) <ul><li>NEUROTRANSMITTER SYSTEMS I </li></ul><ul><li>Neurotransmitters </li></ul><ul><li>Acetylcholine </li></ul><ul><li>The Monoamines </li></ul><ul><ul><ul><li>• Dopamine </li></ul></ul></ul><ul><ul><ul><li>• Norepinephrine </li></ul></ul></ul><ul><ul><ul><li>• Serotonin </li></ul></ul></ul>
  195. 197. Neurotransmitters and Neurohormones • Neurotransmitters – substances released by one neuron that bind to receptors on the target neuron e.g., acetylcholine note: some are referred to as Neuromodulators • Neurohormones – released by brain or other organs, travel via bloodstream to target neurons e.g., epinephrine (adrenal gland)
  196. 198. Neurohormone Release of epinephrine from the adrenal gland produces sympathetic arousal
  197. 199. Examples of Neurotransmitters in the Brain <ul><li>Acetylcholine </li></ul><ul><li>Dopamine </li></ul><ul><li>Norepinephrine </li></ul><ul><li>Serotonin </li></ul><ul><li>Glutamate </li></ul><ul><li>GABA </li></ul><ul><li>Anandamide </li></ul>
  198. 200. Neurotransmitter Associated Neurons Acetylcholine cholinergic Dopamine dopaminergic Norepinephrine noradrenergic Serotonin serotonergic Epinephrine adrenergic Glutamate glutaminergic GABA GABAergic Anandamide cannabinergic Names of Neurons Associated with Specific Neurotransmitters
  199. 201. Acetylcholine • First neurotransmitter discovered (in PNS) • Most extensively studied neurotransmitter
  200. 202. Cholinergic Neurons 1. Dorsolateral Pons ––––––– REM sleep (including atonia) 2. Basolateral Forebrain –––– Activates cerebral cortex (nucleus basalis) facilitates learning & memory 3. Medial Septum ––––––––– Controls rhythms in hippocampus modulates memory formation
  201. 203. Synthesis of Acetylcholine Produced by combining the lipid breakdown product choline with acetyl-CoA (made in the mitochondria)
  202. 204. Synthesis of Acetylcholine
  203. 205. Enzymes Enzymes are proteins that catalyze a reaction that might normally take a long time to occur. If you see a word ending in “ –ase ” it’s an enzyme. The first word or part of the word (if it’s a one-word name) refers to what the enzyme is acting on. For example : • Choline acetyltransferase acts on choline to transfer an acetyl group and thus convert it to acetylcholine • Acetylcholinesterase acts on acetylcholine to break it up.
  204. 206. Two Types of ACh Receptors <ul><li>Ionotropic ––– Nicotinic AChRs (fast) </li></ul><ul><li>Metabotropic – Muscarinic AChRs (slow) </li></ul>
  205. 207. Cholinergic Receptors • Muscles contain nicotinic AChRs ( essential for rapid transmitter action at neuromuscular junction! ) • CNS contains both types, though mostly muscarinic AChRs ( nicotinic AChRs tend to be found at axoaxonic synapses )
  206. 208. Breakdown & Local Synthesis of ACh Acetylcholinesterase – Inactivates ACh after it is released (AChE) (breaks it into acetate and choline) Choline Re-uptake ––– Choline is transported back into the presynaptic terminal for local synthesis of ACh. Re-uptake is vital because axonal transport of choline from cell body is slow! Re-uptake has an efficiency of ~50% (i.e., about half of released is recovered)
  207. 209. Breakdown & Local Synthesis of ACh
  208. 210. Acetylcholinesterase ( located in the synaptic cleft ) breaks down acetylcholine into acetate and choline (which is recycled). Hemicholinium is a drug that inhibits the reuptake of choline. Reuptake has an efficiency of 50% (i.e., 50% is reused)
  209. 211. Drugs that Affect Cholinergic Receptors Examples 1. Curare • Blocks nicotinic AChRs (or nAChRs) • Had been and still is used by native South American populations • Used to paralyze muscles during surgery 2. Atropine • Blocks muscarinic AChRs (or mAChRs) • Used to treat AChE inhibitors (thus reducing the excess ACh action) • Also used to dilate the pupils for eye exams
  210. 212. Toxins that Affect Cholinergic Transmission Examples 1. Botulinum toxin ––––––––––––– Clostridium botulinum Prevents release of ACh thus it blocks muscle excitation VERY POTENT! (e.g., 1 oz can kill 200 million people!) 2. Tetanus toxin ––––––––––––––– Clostridium tetani Prevents release of Glycine & GABA thus it blocks inhibitory transmission indirectly causing excess ACh release Botulinum and Tetanus toxins cleave Synaptobrevin (thus preventing vesicle fusion & transmitter release) 3. Black Widow Spider Venom ––– Stimulates ACh release less toxic, but can be fatal in infants and elderly
  211. 213. Drugs that Affect ACh Breakdown Acetylcholinesterase inhibitors (AChE inhibitors) • Prolong the effects of ACh release by preventing its breakdown • Used as insecticides (insects can’t destroy it) • Used medically to relieve symptoms of myasthenia gravis (auto-immune) e.g., neostigmine - AChE inhibitor that can’t cross blood-brain barrier • Used as biological weapons e.g., Sarin, Tabun (treated with atropine sulfate , discussed earlier, and pralidoxime , which rejuvenates the AChE)
  212. 214. Summary of Cholinergic Drugs Drug Name Drug Effect Effect on Transmission Nicotine Stim nicotinic AChRs AGONIST Curare Block nicotinic AChRs ANTAGONIST Muscarine Stim. muscarinic AChRs AGONIST Atropine Block muscarinic AChRs ANTAGONIST Black widow spider venom Stim. ACh release AGONIST Botulinum toxin Block ACh release ANTAGONIST Neostigmine (can’t cross blood-brain barrier) Blocks acetylcholinesterase AGONIST Hemicholinium Blocks choline reuptake ANTAGONIST
  213. 215. Classification of the Monoamine Transmitters Catecholamines Indolamines Dopamine Serotonin Norepinephrine Epinephrine
  214. 216. Synthesis of dopamine (note DA serves as a precursor for norepinephrine) <ul><li>Tyrosine hydroxylase </li></ul><ul><li>DOPA decarboxylase </li></ul>Add –CH 3 to the NH 2 group to get epinephrine
  215. 217. Dopaminergic Neurons & Projections 1. Substantia Nigra ––––––––– to neostriatum , part of basal ganglia (involved in the control of movement ) 2. VTA ––––––––––––––––– to nucleus accumbens (involved in reinforcing effects of drugs of abuse ) to amygdala (involved in emotions ) to hippocampus (involved in the formation of memories ) 3. VTA ––––––––––––––––– to prefrontal cortex (involved in short-term memories , planning, problem-solving strategies) Nigrostriatal Mesolimbic projection Mesocortical projection
  216. 219. MAO (Monoamine Oxidase) – destroys excess monoamines – MAO-B is specific for dopamine – Deprenyl is an MAO-B inhibitor (depression, Parkinson’s) Reuptake – Transporters are used to remove Dopamine from the synaptic cleft and return it to the nerve terminal Regulation of Dopamine
  217. 220. Drugs that Affect Dopaminergic Transmission Examples 1. Monoamine oxidase inhibitors (MAO inhibitors) • MAO regulates production of catecholamines (destroys excess) • MAO inhibitors are used to treat depression • MAO-B is specific for dopamine (e.g., deprenyl) 2. Re-uptake inhibitors • Blocks re-uptake of dopamine by nerve terminals • e.g., amphetamine , cocaine , methylphenidate (Ritalin) Also causes release of DA & NE by reversing the direction of transporters Also blocks voltage-dependent sodium channels Used to treat ADHD
  218. 221. Examples of Drugs that Affect Dopaminergic Transmission 1. L-DOPA • Used to treat Parkinson’s disease • Crosses blood-brain barrier & enters CNS where it is converted to dopamine 2. AMPT (  -methyl-p-tyrosine) • Binds to tyrosine hydroxylase • Thus it prevents synthesis of L-DOPA and therefore dopamine 3. MPTP (methyl-phenyl-tetrahydropyridene) • Contaminant in synthetic Heroin • It’s metabolized into MPP+, which destroys dopamine neurons and produces Parkinson-like symptoms 4. Reserpine • Prevents storage of monoamines in synaptic vesicles • Acts by blocking transporters that pump monoamines into vesicles • End result is no transmitter is released
  219. 222. Effects of Drugs at Dopaminergic Synapses
  220. 223. Dopamine Receptors • DA receptors are metabotropic • 5 subtypes of DA receptors (D1 – D5) - D1 & D2 are the most common subtypes • Some are autoreceptors (similar to D2) located pre- and post-synaptic - postsynaptic – act to decrease neuron firing (K current) - presynaptic – act to suppress tyrosine-hydroxylase • Apomorphine has multiple effects on DA receptors - At low doses it binds presynaptic autoreceptors (decrease DA) - At high doses it acts as an agonist at postsynaptic D2 receptors
  221. 224. Schizophrenia • Serious mental disorder characterized by hallucinations, delusions, and disruption of normal logical thought processes • May involve hyperactivity of dopaminergic neurons ( excess ) 1. Chlorpromazine ( D2 antagonist ) alleviates hallucinations in schizophrenic patients 2. Clozapine ( D4 antagonist ) also relieves symptoms
  222. 225. Summary of Dopaminergic Drugs Drug Name Drug Effect Effect on Transmission L-DOPA Stimulate DA synthesis AGONIST AMPT Inhibit DA synthesis ANTAGONIST Deprenyl MAO-B inhibitor AGONIST Reserpine Block storage of DA in synaptic vesicles ANTAGONIST Amphetamine, Cocaine, Methylphenidate All 3 Block DA reuptake AGONIST MPTP Destroys DA neurons ANTAGONIST Clorpromazine Blocks D2 receptors ANTAGONIST Clozapine Blocks D4 receptors ANTAGONIST
  223. 226. Noradrenergic Neurons Locus Coeruleus (located in Reticular Formation) • Contains noradrenergic neurons whose axons extend to most of the brain, including thalamus, hypothalamus, limbic, cerebral cortex • Activation of LC increases vigilance or attentiveness to environment
  224. 227. Norepinephrine • Synthesized from dopamine • Synthesis actually occurs inside synaptic vesicles
  225. 228. Synthesis of dopamine and norepinephrine Add –CH 3 to the NH 2 group to get epinephrine <ul><li>Tyrosine hydroxylase </li></ul><ul><li>DOPA decarboxylase </li></ul><ul><li>Dopamine b-hydroxylase </li></ul>
  226. 229. Examples of Drugs that Affect Noradrenergic Transmission 1. Fusaric acid • Blocks DA-  -hydroxylase • Results in blockade of NE production in vesicles 2. Moclobemide • Blocks MAO-A (which normally destroys excess NE) • Results in an increase in NE 3. Desipramine • Blocks re-uptake of NE (and possibly serotonin) • a tricyclic antidepressant
  227. 230. Noradrenergic Receptors • NE receptors are called adrenergic because they respond to both norepinephrine (nor adren alin) and epinephrine ( adren alin) • Adrenergic receptors are metabotropic and coupled to G proteins • 2 types of adrenergic receptors are alpha (  ) and beta (  ) -  1 - and  2 -adrenergic (located in CNS & PNS) -  1 - and  2 -adrenergic (located in CNS & PNS) -  3 (located only in PNS) •  1 -adrenergic (slow depolarizing effect; more responsive to excitatory input) •  2 -adrenergic (slow hyperpolarizing effect) •  1 - and  2 -adrenergic are excitatory (they increase neuronal responsiveness to inputs).  1 are mostly on heart muscle whereas  2 are mostly on smooth muscle lining bronchioles & arterioles of skeletal muscle. Example of contraindications: beta-blockers & hypertension in asthmatics!
  228. 232. Summary of Noradrenergic Drugs Drug Name Drug Effect Effect on Transmission Clonidine – has a calming effect (but also interferes with learning) Yohimbine – has an agitating effect; promotes anxiety Clonidine Stimulate  2 receptors AGONIST Yohimbine Block  2 receptors ANTAGONIST Albuterol Stimulate  2 receptors AGONIST Butoxamine Block  2 receptors ANTAGONIST Fusaric acid Inhibits NE synthesis ANTAGONIST Reserpine Inhibits storage of NE in vesicles ANTAGONIST Desipramine Inhibits reuptake of NE AGONIST Moclobemide Inhibits MAO-A AGONIST
  229. 233. END – Lecture 08
  230. 234. PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 09 (October 06, 2010) <ul><li>NEUROTRANSMITTER SYSTEMS II </li></ul><ul><li>The Monoamines ( continued …) </li></ul><ul><ul><ul><li>• Serotonin </li></ul></ul></ul><ul><li>Amino Acids as Neurotransmitters </li></ul><ul><ul><li>• glutamate, GABA, glycine </li></ul></ul><ul><ul><li>• NMDA receptors & GABA receptors </li></ul></ul><ul><li>Other Neurotransmitters & Neuromodulators </li></ul><ul><ul><ul><li>• peptides, lipids, nucleosides, soluble gases </li></ul></ul></ul>
  231. 235. Serotonin • Synthesized from the amino acid tryptophan • Important in the following: - regulation of mood - control of eating, sleep, arousal - regulation of pain ( hyperalgesia after injury) - control of dreaming
  232. 236. Serotonin • PRECURSORS to serotonin Dorsal Raphe –– sends 5-HT projections to cortex & basal ganglia • Medial Raphe –– sends 5-HT projections to cortex & dentate gyrus Note: raphe means “crease” or “seam” (the nuclei are found near the midline of the brain stem) The clusters of nuclei that make up the raphe are found in the medulla, pons, and midbrain.
  233. 237. Synthesis of Serotonin (or 5-HT) PCPA ( p -chlorophenylalanine) • blocks tryptophan hydroxylase and thus serotonin production MAO-A (monoamine oxidase A) • inactivates excess serotonin • ultimately converted into 5-HIAA ( measureable metabolite ) (5-hydroxy-indoleacetic acid)
  234. 238. Serotonin Receptors • 5-HT receptors are metabotropic ( except 5-HT 3 is an ionotropic Cl - channel ) • At least 9 different subtypes of 5-HT receptors - 5-HT 1A-1B ; 5-HT 1D-1F ; 5-HT 2A-2C ; 5-HT 3 - 5-HT 1B and 1D are presynaptic autoreceptors (axons) - 5-HT 1A are presynaptic autoreceptors (soma & dendrites) • 5-HT 3 are important in nausea & vomiting (antagonists help in chemo patients) Reminder: an autoreceptor is a receptor on its own axon terminal that responds to the neurotransmitter released by the same axon (a negative feedback mechanism)
  235. 239. Drugs that Affect Serotonin • 5-HT re-uptake inhibitors ( SRIs or SSRIs ) are useful in treating certain mental disorders (these drugs act by prolonging the action of serotonin at synapses) e.g., Fluoxetine (Prozac) - depression & anxiety disorders • Drugs that stimulate 5-HT release have also been used e.g., Fenfluramine – has been used as an appetite suppressant (in combination with phenteramine which acts on catecholamines to counteract the drowsiness caused by fenfluramine) • 5-HT 2A agonists cause hallucinations e.g., LSD is thought to exert behavioral effects as an agonist of 5-HT 2A receptors in the forebrain • Ecstasy ( MDMA ; 3-4 methylenedioxymethamphetamine ) causes release of serotonin, norepinephrine, and to a lesser extent dopamine (agonistic effect). MDMA damages serotonergic neurons .
  236. 240. Summary of Serotonergic Drugs Drug Name Drug Effect Effect on Transmission Fenfluramine Stimulate 5-HT release AGONIST Fluoxetine Inhibits reuptake of 5-HT AGONIST PCPA Inhibits 5-HT synthesis ANTAGONIST Reserpine Inhibits storage of 5-HT in vesicles ANTAGONIST
  237. 241. Summary of Neurotransmitter Synthesis Pathways PKU (phenylketonuria) - myelination - brain damage
  238. 242. Amino Acid Neurotransmitters Two Major Classes: excitatory and inhibitory 1. The Excitatory Neurotransmitter is Glutamate (in brain & spinal cord) 2. The Inhibitory Neurotransmitter is GABA (in brain) or Glycine (in spinal cord and lower brain)
  239. 243. Amino Acid Neurotransmitters <ul><li>GLUTAMATE (PRINCIPLE EXCITATORY TRANSMITTER) </li></ul><ul><li>• 4 receptor subtypes ( 3 ionotropic & 1 metabotropic ) </li></ul><ul><ul><li>AMPA receptor (ionotropic) is the most common (Na + influx). These ionotropic receptors bind glutamate and open ion channel, even when the cell is at rest. </li></ul></ul><ul><ul><li>NMDA receptor (ionotropic) is also common but these require depolarization because they are blocked by Mg 2+ when neuron is at rest (see next slide). </li></ul></ul><ul><li>• caffeine increases glutamate indirectly by blocking adenosine receptors which normally inhibit glutamate release </li></ul><ul><li>• MSG (monosodium glutamate) binds glutamate receptors and can produce tingling, burning, ringing in the ears, loss of sensation </li></ul>
  240. 244. NMDA Receptor Channel Complex 6 NMDAR Binding Sites 1. Glutamate (natural agonist) 2. Glycine (co-agonist required for glutamate to have any effect on NMDARs) 3. Mg 2+ (binds inside channel and blocks) 4. Zn 2+ (decreases activity) 5. Polyamine (increases activity) 6. PCP (blocks channel) Thus, the NMDA Receptor is a Voltage & Neurotransmitter-Dependent Ion Channel
  241. 245. Amino Acid Neurotransmitters GABA (MAJOR INHIBITORY TRANSMITTER IN BRAIN) • 2 main receptor subtypes ( 1 ionotropic & 1 metabotropic ) • [discussed further on next slide] GLYCINE (INHIBITORY TRANSMITTER IN CORD AND LOWER BRAIN) • ionotropic receptors (Cl – influx causes IPSPs) • strychnine is an antagonist (convulsions via excess/uncontrolled excitatatory drive)
  242. 246. GABA Receptors • Enzyme GAD (glutamic acid decarboxylase) converts glutamic acid to GABA - GAD is inhibited by allylglycine (thus blocking GABA synthesis) • GABA receptor subtypes: 1. GABA A • ionotropic • opens Cl – channel, causing Cl – influx and hyperpolarization • [see next slide for more details on GABA receptors] 2. GABA B • metabotropic (coupled to G-proteins) • causes K + efflux and thus hyperpolarization • Baclofen is an agonist (relaxes muscles)
  243. 247. GABA A Receptors GABA A Receptor has 5 binding sites 1. GABA (natural agonist) • muscimol is a direct agonist • bicuculline is a direct antagonist 2. Benzodiazepine (indirect agonist) • anxiolytic drugs (diazepam or valium) tranquilizers, promote sleep, reduce seizure activity, relax muscles 3. Barbiturate (indirect agonist) • low doses have a calming effect • rarely used as anesthetic due to small therapeutic index (easy to OD) 4. Steroid (indirect agonist) 5. Picrotoxin (indirect antagonist) Note:  -CCM (methyl-  -carboline-3-carboxylate) may be a natural ligand for Benzodiazepine binding site. This is an inverse agonist and thus produces fear, tension, and anxiety. It may be part of our fight or flight danger system.
  244. 248. Other Neurotransmitters / Neuromodulators <ul><li>Peptides </li></ul><ul><ul><li>• 2 or more amino acids linked together </li></ul></ul><ul><ul><li>• includes various endogenous opioids </li></ul></ul><ul><ul><li>• Substance P is thought to be the primary neurotransmitter signaling pain </li></ul></ul><ul><li>Lipids </li></ul><ul><ul><li>• can transmit between or within cells </li></ul></ul><ul><ul><li>• e.g., anandamide - endogenous cannabinoid receptor ligand (THC in marijuana binds to the same receptors); altered mood & sensory perception as well as memory and motor impairments </li></ul></ul><ul><li>Nucleosides </li></ul><ul><ul><li>• sugar + purine (A&G) or pyrimidine (C&T) base </li></ul></ul><ul><ul><li>• e.g., adenosine (ribose + adenine) - coupled to G-proteins which open K + channels, thus causing IPSPs (thus it’s inhibitory) </li></ul></ul><ul><ul><li>• caffeine blocks adenosine receptors and thus is excitatory </li></ul></ul><ul><li>Soluble Gases </li></ul><ul><ul><li>• Nitric oxide or NO (NOS converts argenine to NO; blocked by L-NAME) </li></ul></ul><ul><ul><li>• Carbon monoxide or CO </li></ul></ul><ul><ul><li>• diffuse out of the cell and activate neighboring cells to produce cGMP </li></ul></ul>
  245. 249. END – Lecture 09
  246. 250. PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 10 (October 13, 2010) <ul><li>PLASTICITY IN THE NERVOUS SYSTEM </li></ul><ul><li>Neurogenesis </li></ul><ul><li>Origin of brain cells & brain development </li></ul><ul><li>Axon guidance </li></ul><ul><li>Synaptic pruning </li></ul><ul><li>Axonal regeneration </li></ul><ul><li>Denervation supersensitivity </li></ul>
  247. 251. Development of the Human Brain Relative Brain Size: At birth: ~ 350 g At 1 yr: ~1000 g Adult: ~1200 g • Forebrain • Midbrain • Hindbrain
  248. 252. Timeline of Major Stages in Cerebral Cortex Development Neurogenesis declines significantly by week 20 and is nearly complete by 5 mo., but it does continue throughout life in some regions ( i.e., adult neurogenesis ).
  249. 253. Origin of Brain Cells Neurotrophic factors • EGF (epidermal growth factor) – stem to progenitor • bFGF (basic fibroblast growth factor) – progenitor to neuroblast • PDGF (platelet derived growth factor) – progenitor to glioblast (specifically oligodendrocyte)
  250. 254. Brain Development <ul><li>Processes involved in neuron production : </li></ul><ul><li>Proliferation </li></ul><ul><ul><ul><li>– production of new cells ( primitive glia & neurons ) </li></ul></ul></ul><ul><ul><ul><li>– stem cells continue to divide </li></ul></ul></ul><ul><li>Migration </li></ul><ul><ul><ul><li>– occurs inside out </li></ul></ul></ul><ul><li>Differentiation & Maturation </li></ul><ul><ul><ul><li>– formation of axons then dendrites (transplantation depends upon age) </li></ul></ul></ul><ul><li>Myelination </li></ul><ul><ul><ul><li>– continues gradually over many years </li></ul></ul></ul><ul><li>Synaptogenesis </li></ul><ul><ul><ul><li>– formation of synaptic connections ( requires extra cholesterol-from glia ) </li></ul></ul></ul><ul><ul><ul><li>– continues throughout life </li></ul></ul></ul>
  251. 255. Axon Pathfinding (how does an axon know where to go?) Roger Sperry (1943)
  252. 256. Axon Growth and Neuron Survival Growth Cones extend out as axons seek targets Tropic molecules guide axons; produced by targets (e.g., netrins) Trophic molecules support survival of cells and axons once target is reached neurotrophins (e.g., NGF, BDNF) Neuronal and synaptic pruning (via apoptosis) Important concepts : • Chemoattractant • Chemorepellent
  253. 257. Synapse Pruning (Elimination) Synaptic connections are plastic!
  254. 258. Effect of Experience on Plasticity <ul><li>Environmental Enrichment </li></ul><ul><ul><li>• Increases dendrite complexity </li></ul></ul><ul><ul><li>• Increases number of synapses </li></ul></ul>
  255. 259. Regrowth of Axons • Can occur as long as the soma or cell body is intact • Rate is usually ~1 mm/day (PNS) • in CNS, axons usually regenerate only 1-2 mm total (CNS) , thus paralysis due to spinal cord injury is usually permanent • In PNS, axon regrowth follows myelin sheath back to target • Regrowth in PNS may not be perfect • e.g., if a motor neuron’s axon is cut (not crushed), segments may not align and axon may synapse on wrong target muscle
  256. 260. Collateral Sprouting
  257. 261. Denervation Supersensitivity Remember: Amphetamine causes DA release from existing axon terminals Apomorphine stimulates DA receptors (an appropriately high dose was used)
  258. 262. END – Lecture 10
  259. 263. <ul><li>MUSCLES & SPINAL REFLEXES </li></ul><ul><li>Muscle Cell Types and Muscle Fibers </li></ul><ul><li>Skeletal Muscles and Movement </li></ul><ul><li>Spinal Reflexes </li></ul><ul><ul><li>• Spinal cord </li></ul></ul><ul><ul><li>• Withdrawal reflex </li></ul></ul><ul><li>Extrafusual vs. Intrafusal Muscle Fibers </li></ul><ul><ul><ul><li>• Stretch reflex </li></ul></ul></ul><ul><ul><ul><li>• Reciprocal innervation </li></ul></ul></ul><ul><ul><ul><li>• Tendon reflex </li></ul></ul></ul><ul><li>Crossed Extensor Reflex </li></ul>PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 11 (October 18, 2010)
  260. 264. Muscles and Muscle Fibers
  261. 265. 3 Types Muscle
  262. 266. Muscles and Muscle Fibers Skeletal Muscle : • Attach to bone or cartilage via tendons • Made up of cells (muscle fibers) • Each muscle fiber contains contractile proteins Actin – thin filaments Myosin – thick filaments • The filaments overlap
  263. 267. Major Components of Skeletal Muscle
  264. 268. Skeletal Muscle : • Striated appearance due to arrangement of actin & myosin • Actin filaments (thin) are attached to proteins that form the Z-line • Myosin filaments (thick) are found between rows of actin Sliding Filament Theory of Muscle Contraction • During contraction , the following events occur: 1. Actin filaments slide along each myosin filament (from both ends) 2. Z-lines get closer together (because actin is attached to Z-line) 3. Result is that the muscle shortens
  265. 269. Sliding Filament Theory
  266. 270. Neuromuscular Junction & Muscle Contraction : • Motor neurons innervate skeletal muscle fibers at a special region called the motor endplate • The motor endplate contains ACh receptors (mostly nicotinic) • One motor neuron can innervate multiple muscle fibers Motor Unit = motor neuron plus the muscle fibers it innervates • Muscles used for very fine (discrete) movements have smaller motor units • Muscles used for posture have larger motor units
  267. 271. Classification of Skeletal Muscles by Color : Red Muscle – High concentration of myoglobin (carries oxygen) – Relies heavily on oxidation to produce ATP – Engages in heavy activity without fatiguing – Used for slow, sustained movements – e.g., chicken or turkey legs White Muscle – Low concentration of myoglobin – Quickly goes into oxygen debt during contraction – Fatigues quickly – Used for rapid contractions in short bursts – e.g., chicken or turkey breasts Note: In humans and other mammals, red and white muscle fibers are found in the same muscles, unlike birds. For example, sprinting uses white, hiking/walking uses red.
  268. 272. Antagonistic Muscles (flexion and extension) Isotonic Contraction (muscle shortens) e.g., legs, produces the movement when carrying heavy box Isometric Contraction (muscle length stays same) e.g., back & arm muscles contract when holding or carrying heavy box Think of the different muscles that are used when carrying a heavy box up a flight of stairs – some contractions are isotonic and some are isometric. Muscular Movements and Contractions
  269. 273. Opposing or Antagonistic Muscle Movements Antagonistic Muscles (flexion vs extension)
  270. 274. Spinal Control of Movement REFLEXES are rapid movements mediated by either brain stem nuclei or the spinal cord (we’ll only cover spinal cord today). They are very Important (e.g., protect the body, basic life support) They vary in complexity and number of synapses: • Simple (e.g., withdrawal or flexion reflex) • Complex (e.g., postural, involving many different muscles) Note: Simple and Complex are relative terms. Even simple reflexes can involve MANY neurons (even thousands).
  271. 275. Three Reflexes Seen in Infants • Grasping • Babinski • Rooting
  272. 276. The Babinski Reflex – in children & adults it’s diagnostic of CNS damage • Positive Babinski – fanning of toes with stroking bottom of foot – always seen in infants < ~6 mo. (due to lack of descending inhibition) • Negative Babinski – curling of toes with stroking bottom of foot – seen in older infants and all healthy people – results from descending inhibitio n from brain
  273. 277. Withdrawal Reflex is a simple reflex involving only a few synapses between the sensory (afferent) neuron and the motor (efferent) neuron
  274. 278. Withdrawal Reflex (involves one or more interneurons between the sensory and motor neuron) Note: the more interneurons (and thus synapses) there are in the reflex arc, the longer the reflex takes
  275. 279. Withdrawal Reflex Note: descending projections from the brain can inhibit reflexes
  276. 280. 2 Types of Motor Neurons <ul><li>Alpha motor neurons </li></ul><ul><ul><ul><li>• larger diameter </li></ul></ul></ul><ul><ul><ul><li>• faster conduction time </li></ul></ul></ul><ul><ul><ul><li>• innervate extrafusal muscle fibers </li></ul></ul></ul><ul><li>Gamma motor neurons </li></ul><ul><ul><ul><li>• smaller diameter </li></ul></ul></ul><ul><ul><ul><li>• slower conduction time </li></ul></ul></ul><ul><ul><ul><li>• innervate intrafusal muscle fibers </li></ul></ul></ul><ul><ul><ul><li>• important for enabling muscle spindle to provide a readout of muscle length ( see gamma motor neuron slide ) </li></ul></ul></ul>
  277. 281. Extrafusal fibers run the length of the muscle Intrafusal fibers do not run the length of the muscle and are located within the muscle spindle Note that the downward movement of the arm activates stretch reflex, which increases the strength of the muscle contraction and pulls the arm back up Monosynaptic Stretch Reflex
  278. 282. Examples • Patellar tendon reflex • Head bobbing upward when falling asleep while sitting in a chair Monosynaptic Stretch Reflex
  279. 283. Intrafusal muscle fibers Muscle Spindle – A few intrafusal fibers joined to a nuclear bag (inside the nuclear bag is a stretch receptor called the Annulospiral Receptor ). Axons from annulospiral receptor terminate onto motor neurons in spinal cord . Thus, stretching a muscle activates the annulospiral receptor which then stimulates extrafusal fibers to contract that same muscle. The Muscle Spindle (or annulospiral receptor) is vital for maintaining muscle tone Think of it like a “spring” located inside the muscle.
  280. 284. Gamma Motor Neurons Notice that if the muscle length changes due to muscle contraction (b) , the muscle spindle is “off line” and unable to respond to changes in muscle length. Activation of gamma motor neuron contracts the intrafusal fibers and thus “resets” the spindle so it can once again respond to stretch (c) .
  281. 285. Problem inherent in the stretch reflex • Contraction of one muscle would produce contraction of antagonist muscle • For example, the simple bending of the arm by biceps contraction (agonist) would cause the arm to straighten due to activation of the stretch reflex of triceps (antagonist) muscle Solution: Reciprocal Innervation (discovered by Sherrington). With reciprocal innervation, the axons of motor neurons that synapse on a muscle also branch and activate interneurons that inhibit motor neurons that synapse on the antagonist muscles.
  282. 286. Reciprocal Innervation Prevents the simple bending of an arm (biceps contraction) from causing the arm to straighten due to stretch reflex of the antagonistic triceps muscle
  283. 287. What if the muscle is contracting too vigorously? Golgi Tendon Organ Reflex is activated Golgi Tendon Organ (GTO) – stretch receptor found in the tendon – provides feedback to nervous system about muscle contraction – GTO fires when stretched – GTO axons synapse onto inhibitory spinal cord neurons – result of GTO activation is inhibition of the motor neuron – prevents damage to muscle as a result of excess contraction
  284. 288. Golgi Tendon Organ Reflex Think of the GTO like a “spring” located at each end of the muscle (in the tendon)
  285. 289. Proprioceptors (stretch receptors)
  286. 290. Sir Charles Scott Sherrington (1884-1935) • Studied many kinds of reflexes • Discovered reciprocal innervation • Introduced the term synapse • Principle of the Common Path – motor neuron is final common path for all movement • Principle of the Integrative Action of Neurons – all neurons in the body work together to produce smooth, precise movement – the crossed extensor reflex is an excellent example
  287. 291. Crossed Extensor Reflex • Withdrawal Reflex activated by sensory neuron synapsing onto interneuron, which excites motor neurons of the ipsilateral flexor • Interneuron also crosses over and synapses onto and excites the motor neurons of the contralateral extensor Example - if you step on a tack while walking, you’ll fall down without this reflex
  288. 292. END – Lecture 11
  289. 293. <ul><li>CONTROL OF MOVEMENT BY THE BRAIN </li></ul><ul><li>Anatomical Considerations </li></ul><ul><ul><ul><li>• upper & lower motor neurons </li></ul></ul></ul><ul><ul><ul><li>• motor cortex </li></ul></ul></ul><ul><li>Two Major Motor Systems </li></ul><ul><ul><ul><li>• Pyramidal Motor System (lateral system) </li></ul></ul></ul><ul><ul><ul><li>corticospinal tract </li></ul></ul></ul><ul><ul><ul><li>• Extrapyramidal Motor System (medial system) </li></ul></ul></ul><ul><ul><ul><li>basal ganglia & cerebellum </li></ul></ul></ul><ul><li>Effects of Damage to the Descending Motor System </li></ul><ul><ul><ul><li>• corticospinal tract damage </li></ul></ul></ul><ul><ul><ul><li>• basal ganglia and cerebellar damage </li></ul></ul></ul>PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 12 (October 20, 2010)
  290. 294. Classification of Neurons Associated with the Motor System <ul><li>Upper Motor Neurons </li></ul><ul><ul><ul><li>• above level of spinal cord motor neurons </li></ul></ul></ul><ul><ul><ul><li>• e.g., cortical neurons </li></ul></ul></ul><ul><li>Lower Motor Neurons </li></ul><ul><ul><ul><li>• spinal cord motor neurons </li></ul></ul></ul><ul><ul><ul><li>• e.g., those in ventral horn of spinal cord </li></ul></ul></ul>
  291. 295. Motor Cortex & Motor Homunculus 1 2 3 4
  292. 296. Classification of Descending Motor Systems <ul><li>The Lateral Group or System ( fine or directed movements ) </li></ul><ul><ul><ul><li>• lateral corticospinal tract ( dorsolateral tract ) </li></ul></ul></ul><ul><li>The Medial Group or System ( automatic or postural movements ) </li></ul><ul><ul><li>• anterior corticospinal tract ( ventromedial tract ) </li></ul></ul><ul><ul><li>• basal ganglia & cerebellum </li></ul></ul>Contemporary Classification Scheme
  293. 297. The Lateral (Pyramidal) Motor System Originates in the Primary Motor Cortex (precentral gyrus) Axons of these Upper Motor Neurons project downward • through internal capsule • through medullary pyramids (hence name) • main branch crosses over at pyramidal decussation in medulla and descends through the contralateral spinal cord forming the lateral corticospinal tract
  294. 298. Lateral Corticospinal Tract • fine, directed motor control • hands, fingers, feet, toes • synapse directly onto motor neurons or indirectly via interneurons
  295. 299. Effects of Damage to Corticospinal Tract Damage to the Corticospinal Tract at any Level produces: 1. Initial loss of muscle tone ( atonia ) • transient flaccid paralysis immediately upon damage 2. Hyperactive deep tendon reflexes (myotactic) • hyperreflexia 3. Appearance of the Babinski sign ( positive Babinski ) • note: a positive Babinski may be seen during sleep or intoxication, and in infants <~6mo. Thus, appearance of a positive Babinski sign is diagnostic of pyramidal tract damage.
  296. 300. Effects of Cortical Damage to Lateral System Damage to the Premotor or Supplementary Motor Cortex or to parts of the Parietal or Temporal cortex produces Apraxia Apraxia “without action” – Difficulty carrying out purposeful movements, in the absence of paralysis or muscle weakness Apraxias are classified according to the systems affected: limb apraxia – movement (parietal lobe damage) (e.g., difficulty if asked to demonstrate a movement) oral apraxia – speech (Broca’s area damage) apraxic agraphia – writing (left parietal lobe damage if right-handed) constructional apraxia - drawing or construction (parietal lobe damage) (e.g., difficulty with spatial perception and execution) NOTE: Apraxias DO NOT involve damage to primary motor cortex or any other lower portions of the lateral motor system
  297. 301. Cortical Control of Movement Posterior association cortex is involved with perceptions Frontal association cortex is involved with plans for movement
  298. 302. Motor Neuron Disorders Muscular Dystrophy – muscle wasting • 30 different types, Duchenne’s MD is the most common - about 1 in 3-4000, typically between ages of 2 and 6 - due to defect in gene that encodes dystrophan - more common in boys (due to gene on X-chromosome) Myasthenia Gravis – degeneration of acetylcholine receptors at NMJ • results from an autoimmune response against AChRs • treated with immunosuppressants or thymectomy • treated with anticholinesterases (acetylcholinesterase inhibitors) • may also try plasmapheresis (filter the AChR-attacking antibodies from the patient’s blood) Amyotrophic lateral Sclerosis or ALS (Lou Gehrig’s disease) – motor neuron degeneration • degeneration of motor neurons in brain and spinal cord • progresses from muscle weakness to muscle wasting • no treatment • ~5,600 new cases each year, typically between ages of 40 & 70
  299. 303. The Medial (Extrapyramidal) Motor System Coordinates gross movements & postural adjustments • Develops before the pyramidal (lateral) system e.g., babies can play patty-cake before learning to hold a crayon • Develops at different times e.g., babies can hold head up before sitting upright
  300. 304. The Medial (Extrapyramidal) Motor System <ul><li>Brain Regions </li></ul><ul><li>Cerebellum </li></ul><ul><ul><ul><li>• Receives sensory information from all sensory systems and cortex </li></ul></ul></ul><ul><ul><ul><li>• It must know what every muscle in the body is doing at every moment </li></ul></ul></ul><ul><ul><ul><li>• Ballistic movements, learned movements </li></ul></ul></ul><ul><li>Basal Ganglia </li></ul><ul><ul><ul><li>• Relays info to and from cerebral cortex </li></ul></ul></ul><ul><ul><ul><li>• Numerous structures work together to coordinate gross movements </li></ul></ul></ul>Some drugs (e.g., classical antipsychotics) act to decrease dopamine activity in the brain. Thus, these drugs may have “ extrapyramidal side effects ” , which include tremors, rigidity, and a shuffling gait
  301. 305. The Cerebellum and Movement Note: The cerebellum may contain ~50 billion neurons, compared with ~22 billion neurons in the cerebral cortex! <ul><li>• important for rapid coordination of movements </li></ul><ul><li>• important for ballistic movements </li></ul><ul><li>• receives information from all senses and cerebral cortex </li></ul><ul><li>• must know what every muscle is doing at any given time in order to properly coordinate rapid movements </li></ul><ul><li>• damage results in a variety of impairments: </li></ul><ul><li>ataxia – inability to walk in a coordinated manner </li></ul><ul><ul><li>disequilibrium – loss of balance </li></ul></ul>
  302. 306. Basal Ganglia – a cluster of neuronal structures concerned with the production of movement. <ul><li>Striatum ( Caudate , Putamen ) </li></ul><ul><ul><ul><li>• receives information from cerebral cortex </li></ul></ul></ul><ul><ul><ul><li>• sends that information to Globus Pallidus </li></ul></ul></ul><ul><ul><ul><li>• caudate – process of cognitive information </li></ul></ul></ul><ul><ul><ul><li>• putamen – relays motor signals </li></ul></ul></ul><ul><li>Globus Pallidus </li></ul><ul><ul><ul><li>• sends information back to cortex via thalamus </li></ul></ul></ul><ul><li>Substantia Nigra </li></ul><ul><ul><ul><li>• produces DA and projects to caudate and putamen </li></ul></ul></ul><ul><li>Subthalamic Nucleus (STN) </li></ul><ul><ul><li>• sends projections to and receives projections from the globus pallidus </li></ul></ul>
  303. 307. Location of the Basal Ganglia within the Forebrain
  304. 308. Damage to the Basal Ganglia Basal ganglia damage results in movement disorders Tics – brief, involuntary contractions of specific muscles Choreas – involuntary movements of head, arms, legs Huntington’s disease – uncontrolled tics and choreas early, dementia later – disruption of gene on chromosome 4 (excess CAG repeat) resulting in an abnormal Huntingtin ( Htt ) protein (with an elongated string of glutamine residues on it). The Htt mutation ultimately leads to death of GABAergic inhibitory neurons in the putamen (part of striatum) Parkinson’s disease – tremor, loss of balance, rigidity (hard to initiate movement) – caused by loss of dopaminergic neurons in substantia nigra
  305. 309. Relationship Between CAG Repeats and Age of Onset • CAG codes for glutamine • 11-24 CAG repeats is normal • >36 is linked to Huntington disease
  306. 310. Brain of Patient with Huntington’s Disease
  307. 311. Treatments for Parkinson’s Disease 1. Pharmacological Treatments L-DOPA – crosses blood-brain barrier and is converted to dopamine glutamate antagonists – reduce hyperactivity of glutamate in subthalamic nucleus 2. Destructive Surgical Treatments thalamotomy – surgical cut in ventral thalamus pallidotomy – surgical cut through the globus pallidus • both are thought to interfere with excitatory messages that produce symptoms • both reduce the rigidity and tremors (improving posture, gait, locomotion) • cognition and mood may also be improved with pallidotomy 3. Nondestructive Surgical Treatments subthalamic nucleus (STN) stimulation reduces symptoms • also called deep brain stimulation 4. Restorative Surgical Treatments fetal stem cell implantations – insertion of DA-producing cells from dead fetuses • raises serious ethical issues ( adult stem cells may be better, especially from same patient ) gene therapy – introduction of a gene that would rescue function • e.g., use virus to deliver GAD gene to STN, thus restoring lost inhibition
  308. 312. END – Lecture 12
  309. 313. <ul><li>THE VISUAL SYSTEM I </li></ul><ul><li>Electromagnetic Spectrum & Waves </li></ul><ul><li>Anatomy of the Eye </li></ul><ul><li>Eye anatomy and blindspot </li></ul><ul><li>Visual Receptors </li></ul><ul><ul><ul><li>• rods </li></ul></ul></ul><ul><ul><ul><li>• cones </li></ul></ul></ul><ul><li>Cells of the Retina </li></ul><ul><li>Effects of light stimulation on transmission through retina </li></ul>PHYSIOLOGICAL PSYCHOLOGY (PSY 254) Lecture 12 (October 20, 2010)
  310. 314. Many Stimuli are Transmitted as Waves (e.g., electromagnetic radiation, vibration, and sound) The Electromagnetic Spectrum 1. Wavelength (nm, 1 nm = 10 -9 m) 2. Frequency (Hz, Hertz, cycles per s) 3. Amplitude (dB, decibels, range: 0 to 160) Wavelength ~380-760 nm is visible to humans Q: Why is the sky blue during day but reddish at sunrise or sunset?
  311. 315. v = ƒ  Electromagnetic Radiation (e.g., Light Waves) Relationship between velocity ( v ) , frequency (ƒ) , and wavelength (  ) of light can be described by the following equation: • Don’t worry about doing any calculations, this is just an example e.g., blue light with a wavelength of 455 nm (455 x 10 -9 m) would have a frequency of: ƒ = v /  ƒ = (3 x 10 8 m/s) / (455 x 10 -9 m) ƒ = (3/455) x 10 17 / sec ƒ = .00659 x 10 17 Hz ƒ = 659 x 10 12 Hz Notes: speed of light ( v ) is 3 x 10 8 m/s or 186,000 miles/sec m = meters; s = seconds nm = nanometers (10 -9 meters)
  312. 316. Stimulus Intensity is encoded by changes in action potential frequency Adaptation is a decrease in the firing rate in response to a continuous stimulus (e.g., odor perception decreases as you get used to it)
  313. 317. Distribution of Visual Receptors Why is this baby owl’s head nearly upside down?
  314. 318. The Visual System
  315. 319. The

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