Neuroscience

1,361 views

Published on

0 Comments
3 Likes
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
1,361
On SlideShare
0
From Embeds
0
Number of Embeds
13
Actions
Shares
0
Downloads
40
Comments
0
Likes
3
Embeds 0
No embeds

No notes for slide
  • Vision - one of key senses for humans in their day-to-day living.
    Lots of physics involved in vision: we will focus on the first three of these. 1) physics of optics involved in imaging, 2) quantum physics of light absorption by the retina, 3) physics of electrical conduction of nerve impulses, 4) Visual processing in the brain
  • Cajal = father of Neuroscience
    Neuron doctrine = central tenet of modern neuroscience
    Previously believed that the nervous system was a connected meshwork, not made of individual cells
  • Anatomy determined by function
  • Studies on static electricity
    Dissected frog on same table, Frog now dead, using a scalpel, which had picked up a charge, touched sciatic nerve (other end of nerve touching different metal) and dead frogs leg contracted, kicking as if alive.
    Basically found that if touch two ends of muscle with open ends of two different metals that are connected, muscles would contract on dead animal
    Basic idea for battery – weak electrical current produced by crude battery – two metals as electrodes and body fluid as the electrolyte
  • Electrical activity in the body = Motion of positive and negative ions in the body
  • How do neurons generate electrical signals?
  • [A-] = miscellaneous ions and organic ions (proteins)
  • Without pump, Na and K gradients would be highly variable and eventually run down
  • So what happens during the different stages of information transfer and processing in the neuron
  • Depolarization b/c Na normally>> outside cell than in
  • Ion pump keeps the battery charged
  • Neuroscience

    1. 1. Neuroscien ce Crystal Sigulinsky Neuroscience Graduate Program University of Utah crystal.cornett@utah.edu
    2. 2. Housekeeping Notes  Posting lectures online  Writing Assignment  Listed as #4 due Monday July 7th  July 6th = Monday  Office hours  Friday, July 3rd , 5-6 pm, Moran Eye Center 3rd floor lobby  By appointment  Test  Friday, July 10th
    3. 3. Physics in Visual Processes  Imaging in the eye  Optics  Absorption of light in the eye  Quantum mechanics  Nerve conduction  Visual Information Processing http://en.wikipedia.org/wiki/File:Gray722.png Gray's Anatomy of the Human Body, 1918
    4. 4. Neuroscience  Scientific study of the nervous system  Highly interdisciplinary  Structure/function  Development/Evolution  Genetics  Biochemistry  Physics  Physiology  Pathology  Informatics/Computational http://en.wikipedia.org/wiki/Image:Sagittal_brain_MRI.JPG
    5. 5. Objectives  Basic Anatomy of the Nervous System Organization Cells  Neurons Structure Mechanism of function  Modeling neurons  Neurodegenerative Diseases
    6. 6. Nervous System  Multicellular organisms  Specialized cells  Complex information processing system  Innervates the entire body  Substrate for thought and function  Gathers information  External = Organism’s environment  Internal = Organism’s self  Processing  Response initiated  Perception  Muscle activity  Hormonal change
    7. 7.  Central Nervous System (CNS)  Brain  Spinal cord  Peripheral Nervous System (PNS)  Cranial and spinal nerves  Motor and sensory  Somatic NS  “Conscious control”  Autonomic NS  “Unconscious control” http://en.wikipedia.org/wiki/File:Nervous_system_diagram.png Nervous System Anatomy: Gross Organization
    8. 8. http://en.wikipedia.org/wiki/File:NSdiagram.png
    9. 9. Nervous System Anatomy: Cells  Neurons (Nerve Cells) Receive, process, and transmit information  Glia Not specialized for information transfer Primarily a supportive role for neurons
    10. 10. Neurons http://en.wikipedia.org/wiki/Neuron Wei-Chung Allen Lee, Hayden Huang, Guoping Feng, Joshua R. Sanes, Emery N. Brown, Peter T. So, Elly Nedivi http://en.wikipedia.org/wiki/File:Smi32neuron.jpg
    11. 11. Neurons  Neuron Doctrine  Santiago Ramon y Cajal, 1891  The neuron is the functional unit of the nervous system  Specialized cell type  Very diverse in structure and function  Sensory, interneurons, and motor neurons http://en.wikipedia.org/wiki/Santiago_Ram%C3%B3n_y_Cajal Above: sparrow optic tectum Below: chick cerebellum
    12. 12. Neuron: Structure Axon hillock Axon http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png
    13. 13. Neuron: Structure/Function  Specially designed to receive, process, and transmit information  Dendrites: receive information from other neurons  Soma: “cell body,” contains necessary cellular machinery, signals integrated prior to axon hillock  Axon: transmits information to other cells (neurons, muscles, glands)  Polarized  Information travels in one direction  Dendrite → soma → axon Axon hillock http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png
    14. 14. Glia  Major cell type of the Nervous System  ~10X as many glia as neurons  Not designed to receive and transmit information  Do influence information transfer by neurons  Glia = “Glue” (Greek)  Support neurons  Maintain a proper environment  Supply oxygen and nutrients  Clear debris and pathogens  Guide development  Modulate neurotransmission  Myelination
    15. 15. Glia: Types  Macroglia Astrocytes  Regulate microenvironment in CNS  Form Blood-Brain Barrier Oligodendrocytes  Myelinate axons of the CNS Schwann Cells  Myelinate axons of the PNS  Microglia Clean up in the CNS http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png
    16. 16. How do neurons work?  Function Receive, process, and transmit information  Signals Chemical Electrical
    17. 17. Bioelectricity  Electric current generated by living tissue  History http://en.wikipedia.org/wiki/File:Electric-eel2.jpghttp://en.wikipedia.org/wiki/File:Torpedo_fuscomaculata2.jpg Electric Rays (Torpedos) Electric Eels
    18. 18. Bioelectricity  Electric current generated by living tissue  History Electric fish "Animal electricity”  Luigi Galvani, 1786  Role in muscle activity  Inspiration behind Volta’s development of the battery http://en.wikipedia.org/wiki/File:Galvani-frog-legs.PNG
    19. 19. Bioelectricity  Electric current generated by living tissues  Motion of positive and negative ions in the body  Essential for cellular and bodily functions  Storage of metabolic energy  Performing work  Cell-cell signaling  Sensation  Muscle control  Hormonal balance  Cognition  Important Diagnostic Tool
    20. 20. How do neurons work?  Function Receive, process, and transmit information Unidirectional information transfer  Signals Chemical Electrical  What is the electrical state of a cell?
    21. 21. Membrane Potential  Difference in electrical potential across cell membrane  Generated in all cells  Produced by separation of charges across cell membrane  Ion solutions  Extracellular fluid  Cytoplasm  Cell membrane  Impermeable barrier  Ion channels  Permit passage of ions through cell membrane  Passive (leaky channels) = with gradient  Active = against gradient  Resting membrane potential  KCl Simple Model
    22. 22. Driving Forces  Chemical driving force Fick’s First Law of Diffusion Species move from region of high concentration to low concentration until equilibrium Passive mechanism  Electrical driving force Charged species in an electric field move according to charge Passive mechanism
    23. 23. Nernst Equation  Calculates the equilibrium potential for each ion R = gas constant, T = temperature, F = Faraday constant, z = charge of the ion Assumptions:  Membrane is permeable to ion  Ion is present on both sides of membrane
    24. 24. Ion Distributions  [Na+] = 15 mM  [K+] = 150 mM  [Cl-] = 9 mM  [A-] = 156 mM  [Na+] = 145 mM  [K+] = 5 mM  [A+] = 5 mM  [Cl-] = 125 mM  [A-] = 30 mM Cytoplasm Extracellular Fluid Cell Membrane - - - - - - - - + + + + + + + +
    25. 25. Driving Forces  Chemical driving force  Fick’s First Law of Diffusion  Species move from region of high concentration to low concentration until equilibrium  Passive mechanism  Electrical driving force  Charged species in an electric field move according to charge  Passive mechanism  Na+/K+ pump  Active transport pump  3Na+ out of cell  2 K+ into cell  Aids to set up and maintain initial concentration gradients
    26. 26. Resting Membrane Potential  Actually 4 ions (K+ , Na+ ,Cl- , Ca2+ ) that strongly influence potential  Goldman-Hodgkin-Katz Equation  Takes into account all ionic species and calculates the membrane potential  P = permeability  Proportional to number of ion channels allowing passage of the ion  Not specific to the resting membrane potential  Can replace p with conductance (G) and [ion]in/[ion]out with Eion  Greater the membrane permeability = greater influence on membrane potential  Permeability: PK: PNa: PCl = 1 : 0.04 : 0.45  Cl- typically not pumped, so at equilibrium  K+ dominates because greatest conductance  Resting membrane potential usually very negative -70 mV
    27. 27. Electric Signals  Deviation in the membrane potential of the cell  Depolarization  Reduction of charge separation across membrane  Less negative membrane potential  Hyperpolarization  Increase in charge separation across membrane  More negative membrane potential  Cause: Ion channels open/close  Large change in permeability of ions relative to each other  Negligible change in bulk ion concentrations!  Induce changes in net separation of charge across cell membrane  Goldman equation only applies to steady state
    28. 28. Electric Signals  Initiated by discrete events Sensory neurons  Examples:  Vision: photoreceptors - absorb light triggering a chemical signaling cascade that opens voltage-gated ion channels  Touch: mechanoreceptors - mechanical pressure or distortion opens stress-gated voltage channels Neuron-neuron, neuron-muscle, neuron-gland  Chemical signals open ligand-gated ion channels at the Synapse
    29. 29. Synapse  Functional connections between neurons  Mediates transfer of information  Allows for information processing  Axon terminal “talks to” dendrite of another neuron  Neurotransmitters activate ligand- gated ion channels http://en.wikipedia.org/wiki/File:Synapse_Illustration2_tweaked.svg
    30. 30. Electric Signals  Deviation in the membrane potential of the cell  Spread according to different mechanisms Electrotonic conduction  Dendrites Action Potential  Axons
    31. 31. Neuron: Structure Axon hillock Axon http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png
    32. 32. Electrotonic Conduction  Passive spread of electrical potential  Induced point increase in ion concentration  Na+ channels opened  Na+ flows into cell  Membrane potential shifts toward Na+ equilibrium potential (positive)  Depolarization  Diffusion of ions  Chemical gradient  Charge (electrical) gradient  Potential dissipates as distance from source increases Na+ ChangeinPotential Distance (x) x = 0
    33. 33. Electrotonic Conduction  Potential dissipates as distance from source increases “Graded Potentials” Summation  Spatially  Multiple sources of ion flux at different locations  Temporally  Repeated instances of ion flux at same location  Allows for information processing
    34. 34. Processing  A single neuron receives inputs from many other neurons Input locations  Dendrites – principle site  Soma – low occurance Inputs converge as they travel through the neuron  Changes in membrane potential sum temporally and spatially http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png
    35. 35. Transmitting Information  Signal inputs do not always elicit an output signal  Change in membrane potential must exceed the threshold potential for an action potential to be produced  Mylenated axons  Axon hillock = trigger zone for axon potential  Unmyelenated axons  Action potentials can be triggered anywhere along axon Axon hillock http://en.wikipedia.org/wiki/File:Action_potential_vert.png http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png
    36. 36. Action Potentials  “All-or-none” principle  Sufficient increase in membrane potential at the axon hillock opens voltage- gated Na+ channels  Na+ influx further increases membrane potential, opening more Na+ channels  Establishes a positive feedback loop  Ensures that all action potentials are the SAME size  Also, complete potential is regenerated each time, so does not fade out  Turned off by opening of voltage gated K+ channels http://faculty.washington.edu/chudler/ap.html http://en.wikipedia.org/wiki/File:Action_potential_vert.png Figure: Ion channel openings during action potential
    37. 37. Action Potential Propagation  Velocity Action potential in one region of axon provides depolarization current for adjacent region  Passive spread of depolarization is not instantaneous  Electrotonic conduction is rate-limiting factor  Unidirectional Voltage gated channels take time to recover  Cannot reopen for a set amount of time, ensuring signal travels in one direction
    38. 38. Transmitting Information  Presynaptic action potential causes a change in membrane polarization at the axon terminals  Votage-modulated Ca2+ channels open  Neurotransmitter is released  Activates ligand- gated ion channels on dendrites of next cell http://en.wikipedia.org/wiki/File:Synapse_Illustration2_tweaked.svg The Synapse
    39. 39. Modeling Neurons  Neurons are electrically active  Model as an electrical circuit Battery  Current (i) generator Resistor Capacitor + - - + Battery Capacitor Resistori - - + + + +
    40. 40. Membranes as Capacitors  Capacitor  Two conductors separated by an insulator  Causes a separation of charge  Positive charges accumulate on one side and negative charges on the other  Plasma Membrane  Lipid bilayer = insulator  Separates electrolyte solutions = conductors http://en.wikipedia.org/wiki/File:NeuronCapacitanceRev.jpg
    41. 41. Ionic Gradients as Batteries  Concentration of ions differ between inside the neuron and outside the neuron  Additionally, Na+/K+ pump keeps these ions out of equilibrium  Ion channels permeate the membrane  Selective for passage of certain ions  Vary in their permeability  Always open to some degree = “leaky”  Net Result: each ionic gradient acts as a battery  Battery  Source of electric potential  An electromotive force generated by differences in chemical potentials  Ionic battery  Voltage created is essentially the electrical potential needed (equal and opposite) to cancel the diffusion potential of the ions so equal number of ions enter and leave the neuron  Establish the resting membrane potential of the neuron
    42. 42. Ion Channels as Resistors  Resistor  Device that impedes current flow  Generates resistance (R)  Ion channels vary in their permeability  “Leaky”  Always permeable to some degree  Permeability is proportional to conductivity  Conductance (g) = 1/R  Ion channels modeled as a battery plus a resistor  Leak channels  Linear conductance relationship, gL  Voltage-gated channels  Non-linear conductance relationship, gn(t,V)
    43. 43. Neuron modeled as an Electrical Circuit Ion pump Created by Behrang Amini http://en.wikipedia.org/wiki/File:Hodgkin-Huxley.jpg
    44. 44. Cable Equation  Describes the passive spread of voltage change in the membrane of dendrites and axons  Time constant (τ)  Capacitor takes time to rearrange charges  Length constant (λ)  Spread of voltage change inhibited by resistance of the cytoplasm (axial resistance)  Spread of voltage limited by membrane resistance (leak channels) http://en.wikipedia.org/wiki/File:NeuronResistanceCapacitanceRev.jpg
    45. 45. Hodgkin-Huxley Model  Describes how action potentials in neurons are initiated and propagated Nrets at en.wikipedia http://en.wikipedia.org/wiki/File:MembraneCircuit.jpg
    46. 46. Neuron Design Objectives  Maximize computing power Increase neuron density Requires neurons be small  Maximize response ability Minimize response time to changes in environment Requires fast conduction velocities
    47. 47. Passive Electrical Properties  Limitations to the design objectives  Action potential generated in one segment provides depolarization current for adjacent segment Membrane is a capacitor  Takes time to move charges Rate of passive spread varies inversely with the product of axial resistance and capacitance  = raCm
    48. 48. Passive Electrical Properties  Membrane Capacitance (C)  Limits the conduction velocity  ΔV = Ic x Δt / C, where Ic = current flow across capacitor, t = time, and C = capacitance  Takes time to unload the charge on a capacitor when changing potential.  Function of surface area of plates (A), distance between plates (d) and insulator properties (ε)  Lipid bilayer = great insulator properties and very thin = high capacitance  Smaller neuron = smaller area = shorter time to change membrane potential = faster conduction velocity
    49. 49. Passive Electrical Properties  Axial resistance (ra) Limits conduction velocity  Ohm’s Law: ΔV = I x ra ra = ρ/πa2  ρ = resistance of cytoplasm, a = cross-sectional area of process Increases with decreasing axonal radius Larger axon = smaller axial resistance = larger current flow = shorter time to discharge the capacitor around axon = faster conduction velocity
    50. 50. Passive Electrical Properties  Input resistance (Rin)  Limits the change in membrane potential  Ohm’s Law: ΔV = I x Rin  Rin = Rm/4πa2  Rm = specific membrane resistance  Function of ion channel density and their conductance  Rin = function of Rm and cross sectional area of process  Smaller axon = fewer channels and smaller area = greater resistance = smaller current for a given membrane potential = longer time to discharge capacitor = slower conduction velocities
    51. 51. Increasing Conduction Velocity  Increase axon diameter  Axial resistance decreases in proportion to square of axon diameter  Capacitance increases in direct proportion to diameter  Net effect  Increased diameter reduces raCm  Increases rate of passive spread  Giant axon of squid  Axon diameter = 1 mm  Limitations:  Need to keep neurons small so can increase their numbers  Energy cost also increases with larger axon diameter
    52. 52. Increasing Conduction Velocity  Myelination of axons  Wrapping of glial membranes around axons  Increases the functional thickness of the axonal membrane  100x thickness increase  Decreases capacitance of the membrane  Same increase in axonal diameter by myelination produces larger decrease in raCm  More effective increase of conduction velocity
    53. 53. Myelin  Lipid-rich substance  Produced by Schwann cells and Oligodendrocytes that wrap around axons  Gaps between = Nodes of Ranvier http://en.wikipedia.org/wiki/File:Neuron-no_labels2.png
    54. 54. Action Potential Propagation  Myelin decreases capacitance  Depolarization current moves quickly  Current flow not sufficient to discharge capacitance along entire length of axon  Length > 1 m  Myelin sheath interrupted every 1-2 mm  Nodes of Ranvier  Exposed bare membrane (~2 um)  Increases capacitance  Depolarization current slows  High density of Na+ channels  Intense depolarization  Regenerates full depolarization of amplitude  Prevents action potential from dying out  Saltatory Conduction  Action potential “hops” from one node of Ranvier to the next, down the axon  Fast in myelinated regions  Slow in bare membrane regions  Ion flow restricted to nodes of Ranvier  Improves energy efficiency  NS uses >20% of body’s metabolic energy!!  High resistance of myelinated membrane reduces current leak  Less work by Na+/K+ pump
    55. 55. Demyelination  Loss of the myelin sheath that insulates axons  Examples:  Multiple sclerosis  Acute disseminated encephalomyelitis  Alexander’s Disease  Transverse myelitis  Chronic inflammatory demyelinating neuropathy  Central pontine myelinosis  Guillain-Barre Syndrome  Result:  Impaired or lost conduction  Neuronal death  Symptoms vary widely and depend on the collection of neurons affected
    56. 56. Multiple Sclerosis  “multiple scars”  Autoimmune condition  Immune system attacks CNS  Kills oligodendrocytes  2-150 affected in 100,000 people  More prevalent in women  Onset in young adults  Physical and cognitive symptoms  Arise from loss of myelination impairing axon conduction  Start as discrete attacks  Progress to chronic problems  Symptoms vary greatly  Changes in sensation  Neuropathic pain  Muscle weakness, spasms, or difficulty moving  Difficulty with coordination and balance  Speech, swallowing or visual problems  Fatigue  Cognitive impairment
    57. 57.  Innervates every part of the body  Hierarchical organization http://en.wikipedia.org/wiki/File:Nervous_system_diagram.png Nervous System Anatomy: Gross Organization
    58. 58. http://en.wikipedia.org/wiki/File:NSdiagram.png
    59. 59. Nervous System Anatomy: Gross Organization  Information processing in the brain is highly parallel  Localization of function  Parallel streams of information in separate tracts and nuclei  Hierarchical processing scheme  Information is relayed serially from one nucleus to the next  Each nucleus performs a specific processing step  More and more abstract information is extracted from the sensory inputs
    60. 60. Neuronal Death  One of few non-regenerating cell populations  Axons can re-grow if cell body survives Target–derived neurotrophic signals  Necessary for survival Barriers to re-growth  Scar tissue  Absence of appropriate developmental guidance signals  Loss of signal  Switch in response to signal
    61. 61. Neurodegenerative Diseases  Ataxia  Conditions causing problems with movements  Cerebellar ataxia  Cerebellum affected – coordination of movements  Sensory ataxia  Dorsal columns affected – diminished sensitivity to joint and body part position  Vestibular ataxia  Vestibular system affected – disequilibrium and vertigo  Dimentia  Conditions affecting cognitive function  Cortical or subcortical areas affected
    62. 62. Alzheimer’s Disease  Most common type of dimentia  Degenerative disease  Terminal  Symptoms vary  Memory loss  Particularly recent memories  Confusion  Anger  Mood swings  Language problems  Long term memory loss  Sufferer eventually withdraws as senses decline  Associated with plaques and tangles in the brain
    63. 63. Parkinson’s Disease  Common type of ataxia  Degenerative, chronic and progressive  Insufficient production of the neurotransmitter dopamine  Reduced stimulation of the motor cortex by the basal ganglia  Characteristic symptoms  Muscle rigidity  Tremor  Slowing or loss of physical movement  Eventually high level cognitive and language problems http://en.wikipedia.org/wiki/File:Sir_William_Richard_Gowers_Parkinson_Disease_sketch_1886.jpg

    ×