Here are the key features of synaptic transmission: - EPSP/IPSP - Excitatory postsynaptic potential caused by sodium influx, inhibitory caused by chloride influx - Summation - Spatial from multiple synapses, temporal from repeated firing overcomes threshold - Synaptic delay - Time for neurotransmitter release, binding and opening of channels - Fatigue - Repeated firing causes depletion of neurotransmitters, reducing response - Role in information processing - Synapses allow complex neural circuits and computations - Drugs - Can enhance or block neurotransmitters, altering synaptic transmission and neural function - Acidosis/alkalosis - Can affect binding of neurotransmitters or opening of ion channels - Hypoxia - Reduces

1. The Nervous System

2. By the end of this lecture you should be
able to:
• Know the general organization of nervous system
• Classify neurons and describe the structure
• Differentiate between anterograde and retrograde
neuronal transport
• Name the glial cells and describe their function
• Know the classification of nerve fibers
• Explain Neuronal response to injury

3. Organization of the Nervous
System
• Central Nervous System (CNS)
• The brain + spinal cord
• The center of integration and control
• Peripheral Nervous System (PNS)
• The nervous system outside of the brain and
spinal cord
• Consists of:
• 31 pairs of Spinal nerves (Carry info to and
from the spinal cord)
• 12 pairs of Cranial nerves (Carry info to
and from the brain)

4. • Autonomic Nervous System (ANS)
- Regulates and controls visceral functions
- Functionally distinct – anatomically
composed of parts of the CNS and PNS
• CNS has 3 parts:
• Sensory system/input-----part of PNS
• Sensory receptors (skin & organs)
• CNS/Centre for Integration
• Brain and Spinal Cord sum up the data received
• Motor system/output-----part of PNS
• nerve impulses from the brain & Spinal Cord -
to effectors (muscles & glands)

11. Peripheral nervous system
Peripheral nervous system
• Sensory afferents
• Motor efferents
Somatic division
Autonomic division

13. • The spinal nerves arise from both sides of the spinal
cord and emerge through the intervertebral foramina.
• Each nerve is formed by the union of a motor and a
sensory nerve root and is, therefore, a mixed nerve.
• Spinal nerve has a contribution from the autonomic
nervous system in the form of a preganglionic fiber

16. What is a neuron?
• Neuron is the name
given to the nerve cell
and all its processes.
• Neurons are excitable
cells that are
specialized for the
reception of stimuli
and the conduction of
the nerve impulse.

17. Neurons
• Neuron structure
• More than 100 billion neurons
• Cell body (soma)
• Nucleus (nucleoli, no centrosome)
• Organelles
• Mitochondria, neurofibrils, golgi apparatus
• Nissle bodies
Rough ER and Golgi apparatus
• Dendrite(s)
• short extensions
• receive signals from sensory receptors or
other neurons

18. • Axon (& axon hillock*)
• conducts nerve impulses
• Long axons called nerve fibers
• Nerve fibers usually covered by myelin
sheath
• Myelin sheath interrupted – Nodes of
Ranvier
• Axons in brain can’t regenerate while
those of PNS can!

19. • Axon hillock:
• Axon hillock & axon differ from soma and
dendrites in that they lack RER, free ribosomes
& GA.
• It is the site where AP is generated because it
has a high conc. of required channels

20. Upper and lower motor neurons
• Upper motor neurons are those neurons that
make up the pyramidal tract (corticospinal
/corticobulbar) and extrapyramidal tract.
• Lower motor neurons are the neurons having
cell bodies located in the ventral horn of the
spinal cord or in certain cranial nerve nuclei.

21. Types of paralysis
• Hemiplegia is paralysis of one side of the body
• Monoplegia is paralysis of one limb only
• Paraplegia is paralysis of both lower limbs
• Quadriplegia is paralysis of all four limbs

22. Axoplasmic Transport
• There is compartmentalization of organelles
inside the neuronTransport type Speed
(mm/day)
Mechanism Material transported
Fast Anterograde ~400 Kinesin (ATP
dependant)
Mitochondria, Vesicles
with peptides/
Nt/enzymes
Fast Retrograde ~200-300 Dynein (ATP
dependant)
Degrdaed vesicular
membrane, absorbed
material (toxins/
viruses/ growth factors)
Slow retrorograde
(more
interruotions)
~0.2-8 Perhaps molecular
motors like above
Cytoskeletal elements
like neurofilament,
actin, proteins

23. Types of Neurons
(Physiological classifiaction)
• Motor neurons
• Take nerve impulses from CNS to muscles or glands
• Multipolar (many dendrites, single axon)
• Cause muscle fibers to contract, glands to secrete
• Sensory neurons
• Take nerve impulses from sensory receptors to CNS
• Unipolar structure
• Extension from the cell body
• divides into a branch that comes to the periphery
and another that goes to the CNS
• both branches are long & myelinated & transmit
nerve impulses
• These branches referred collectively as axon

24. • Interneurons (or association neurons)
• Occur entirely within the CNS
• Typically multipolar
• Communication b/w sensory – motor,
complex circuits (memory, thinking &
language etc)

25. DEPENDING UPON THE
LENGTH OF AXON
• Golgi type 1 neuron
• Golgi type 2 neuron

26. Boron fig 10-3

28. Neuroglia-----not just a glue

29. DIFFERENT TYPES OF GLIAL CELLS
Glial cell type System Location
Fibrous Astrocyte CNS White matter
Protoplasmic
Astrocyte
CNS Grey matter
Ependymal cells CNS Ventricular lining
Oligodendrocytes CNS White matter mainly
Microglia CNS throughout the brain
Satellite cells PNS Sensory and autonomic ganglia
Schwann cells PNS Peripheral axons

30. Astrocyte Functions
• Glue function
• Brain development: Radial astrocytes-their long
processes assist in neuronal migration
• Blood Brain barrier:
• Brain capillaries by tight junctions ( no
pores/holes). Transmembrane transport only
• Astrocytes DONOT physically form BBBthey
do the following:
• Induce tight junction formation
• Participate in cross cellular transport

31. • Nutritive:
• Store all the glycogen which is broken down
to lactate to be aerobically metabolized by
the neurons at the time of increased
metabolic activity
• Help transfer nutrients from blood to neuron

32. Astrocyte Functions

33. Central neuroglial cells
Astrocytes
• Trophic actions
• Maintain ionic environment
• Uptake of neurotransmitter like glutamates
• Blood brain barrier
Oligodendrocytes
• synthesize myelin sheath
Microglia
• have phagocytic actions (macrophages of CNS)
Ependymal cells
• line the ventricles
• Neuronal stem cells

34. Peripheral neuroglial cells
• Schwann cells
• Mylination
• Nerve regeneration
• Satellite cells
• Physical support
• Regulation of chemical environment of ECF

37. General Design of the Nervous
System
• Central Nervous System Neuron: The Basic
Functional Unit
• Sensory Part of the Nervous System-Sensory
Receptors
• Motor Part of the Nervous System-Effectors

38. Processing of Information-"Integrative"
Function of the Nervous System

40. Levels of CNS function
• Spinal cord
• Subcortical
• Cerebral cortex

41. Nervous system and computer

42. Summary
• Nervous system : CNS, PNS, ANS
• CNS: sensory part , center, motor part
• Cells: neurons + neuroglia
• Each neuron: cell body, dendrites, axons
• Classified according to functions, Neuronal projections, numbner
of processes, dendritic pattern
• Glial cells are not simply structural supporting cells. Functions
include nutritive, synaptic modulation, phagocytosis, formation of
CSF, nerve growth factors release, myelination
• Nerves fibers classified according to
• Peripheral neurons may undergo Wallerian degenration and the
axon may grow along its original path- not an option in CNS

43. Synapse
Dr. Sadia Nazir
Assistant Professor Physiology
LMDC

44. By the end of the lecture you
should be able to
• Define and classify synapse
• Discuss steps of synaptic transmission
• Describe intracellular second messenger systems
for synaptic transmission
• Classify neurotransmitters, and know about the
main excitatory and inhibitory ones

45. WHAT IS A SYNAPSE?
DEFINITION:
It is the anatomic site of electrical
communication betweens neurons or neurons
and muscles or glands.

46. SYNAPSE
• Information is transmitted in the
nervous system mainly in the form of
nerve action potentials, called simply
“nerve impulses,”
• Where two neurons come into close
proximity and functional inter neuronal
communication occurs, the site of such
communication is referred to as a
synapse.

47. • The central nervous system contains more than 100 billion
neurons.
• Incoming signals enter this neuron through synapses located
mostly on the neuronal dendrites, but also on the cell body.
• The output signal travels by way of a single axon leaving
the neuron.
• A special feature of most synapses is that the signal
normally passes only in the forward direction

48. Classification:
• Anatomical
• Functional

49. Anatomical classification

50. Anatomical classification
• Axoaxonic synapse
• Axodendritic synapse
• Axosomatic synapse

52. •As many as 100,000 (1 lac)
presynatic terminals on soma
and dendrites combined
•80-95% on dendrites
•5-20% on soma

53. Physiological classification

54. Physiological classification
• On the basis of mode of impulse transmission.
• Chemical
• Electrical

55. CHEMICAL SYNAPSES
Almost all the synapses used for signal transmission in the
central nervous system of the human being are chemical
synapses.
In these, the first neuron or presynaptic neuron secretes
at its nerve ending a chemical substance called a
Neurotransmitter.
This transmitter in turn acts on receptor proteins in the
membrane of the next neuron or post synaptic neuron to
excite the neuron, inhibit it, or modify its sensitivity in
some other way.
Transmission is one-way.

58. CHEMICAL SYNAPSE:
• Presynaptic membrane, cleft, post synaptic
membrane
• One way transmission
• Neurotransmittors
• Excitatory---
• Inhibitory----
• Synapse labelled excitatory or inhibitory

59. Sequence of Events

60. Electrical synapses
• Are characterized by direct open fluid channels
that conduct electricity from one cell to the next.
• Most of these consist of small protein tubular
structures called gap junctions that allow free
movement of ions from the interior of one cell to
the interior of the next.
• Only a few examples of gap junctions have been
found in the central nervous system

62. Physiologic Anatomy of the chemical
Synapse

64. Action of the Transmitter Substance
on the Postsynaptic Neuron—Function of
“Receptor
Proteins”
• The membrane of the postsynaptic neuron
contains large numbers of receptor proteins,
• The molecules of these receptors have two
important components
(1) a binding component
(2) an ionophore component (ion channel or G
protein linked)

65. Ion Channels
The ion channels in the postsynaptic neuronal
membrane are usually of two types:
1. cation channels that most often allow
sodium ions to pass when opened, but
sometimes allow potassium and/or calcium
ions as well,
2. anion channels that allow mainly chloride
ions to pass but also minute quantities of
other anions.

68. “Second Messenger” System in the Postsynaptic Neuron
• There are several types of second messenger
• systems.
• One of the most common types uses a group of proteins
called G-proteins
• prolonged postsynaptic neuronal excitation or inhibition
is achieved by activating a “second messenger”
chemical system inside the postsynaptic neuronal cell
itself, and then it is the second messenger that causes
the prolonged effect.

69. Post synaptic potential
Excitatory
Inhibitory
Depends on the presence of
Receptors in the Postsynaptic Membrane

70. Excitation
 Opening of sodium channels to allow large
numbers of positive electrical charges to flow to the
interior of the postsynaptic cell.
 Depressed conduction through chloride or
potassium channels, or both.
Various changes in the internal metabolism of the
postsynaptic neuron to excite cell activity

71. Inhibition
 Opening of chloride ion channels through the
postsynaptic neuronal membrane
Increase in conductance of potassium ions out of the
neuron
Activation of receptor enzymes that inhibit cellular
metabolic functions that increase the number of
inhibitory synaptic receptors or decrease the number of
excitatory receptors

73. G proteins as second messengers

74. Chemical Synaptic Transmitters
• 2 types:
• Small-molecule, rapidly acting neurotransmitters
• cause most acute responses of the CNS
• Larger molecular size neuropeptides
• cause more prolonged actions, such as long-term
changes in numbers of neuronal receptors, long-term
opening or closure of certain ion channels

75. Types of
Neurotransmitters

76. Small-Molecule, Rapidly Acting
Transmitters
Class I
Acetylcholine
Class II: The Amines
Norepinephrine
Epinephrine
Dopamine
Serotonin
Histamine
Class III: Amino Acids
Gamma-aminobutyric acid (GABA)
Glycine
Glutamate
Aspartate
Class IV

77. Neuropeptide, Slowly Acting Transmitters
or Growth Factors
Hypothalamic-releasing hormones
Thyrotropin-releasing hormone
Luteinizing hormone–releasing hormone
Somatostatin (growth hormone inhibitory factor)
Pituitary peptides
Adrenocorticotropic hormone (ACTH)
Luteinizing hormone
Thyrotropin
Growth hormone
Vasopressin
Oxytocin
Peptides that act on gut and brain
Leucine , enkephalin

78. Synaptic Transmitters
Small molecules
• Acute response
• Short action
• Synthesized in
cytosol of nerve
terminal
• Stored in small
vesicles that are
reused
Neuropeptides
• Slow to act
• Prolonged action
• Synthesized in cell
body
• Stored in large vesicles
that are autolyzed
after release of
neuropeptide

79. FEATURES OF SYNAPTIC TRANSMISSION

80. Students should be able to
• Understand features of synaptic transmission
• Apply or relate the concepts of excitation and
inhibition of synapse with certain clinical
abnormalities

81. Features/properties of Synapse
• EPSP/IPSP
• Fatigue of Synaptic Transmission
• Synaptic delay
• Role of Synapses in Processing Information
• Effect of Acidosis or Alkalosis on Synaptic Transmission
• Effect of Hypoxia on Synaptic Transmission.
• Effect of Drugs on Synaptic Transmission

82. Effect of Synaptic Excitation on the
Postsynaptic Membrane—
Excitatory Postsynaptic Potential.
• shows a presynaptic terminal
• that has secreted a transmitter
into the cleft
• This transmitter acts on the
membrane excitatory receptor
to increase the membrane’s
permeability to Na+.
• sodium ions diffuse rapidly to
the inside of the membrane.

83. EPSP
• This positive increase in voltage above the
normal resting neuronal potential-that is, to
a less negative value-is called the excitatory
postsynaptic potential (or EPSP)
• if this potential rises high enough in the
positive direction, it will elicit an action
potential
• Discharge of a single presynaptic terminal can
never increase the neuronal potential from -65
millivolts all the way up to -45 millivolts.

84. What makes a inhibitory/excitatory
synapse
Excitatory synapse Inhibitory synapse
Opening of sodium channels to allow
large numbers of positive electrical
charges to flow to the interior of the
postsynaptic cell.
Opening of chloride ion channels
through the postsynaptic neuronal
membrane.
Depressed conduction through chloride
or potassium channels, or both.
Increase in conductance of potassium
ions out of the neuron.
Various changes in the internal
metabolism of the postsynaptic neuron to
increase excitatory membrane receptors
or decrease the number of inhibitory
membrane receptors.
Activation of receptor enzymes that
increase the number of inhibitory
synaptic receptors or decrease the
number of excitatory receptors.

86. Summation
Spatial: at same time. Many presynaptic terminals
(EPSP of at least 10-20 mV is required to reach
threshold. One EPSP is usually 0.5 to 1 mV.
• Remember whatever membrane potential change occurs, it
is spread over the entire soma (high electrical
conductivity). It will die in time not over distance)
• Temporal: Same terminal. Many times
When impulse comes- channels open for a millisecond
and close-EPSP/IPSP lasts for 15 msec then dies.
Repeated impulse- channels open again and again- EPSPs
summate before they die-amplify-maybe threshold is
threshold is reached.

87. SPATIAL SUMMATION
• “Spatial Summation” in
Neurons
• many pre synaptic
terminals are usually
stimulated at the same time.
• Even though these
terminals are spread over
wide areas of the neuron,
their effects can still
summate;
• that is, they can add to
one another until neuronal
excitation does occur.

88. TEMPORAL SUMMATION
• Successive discharges
from a single
presynaptic terminal
if they occur rapidly
enough, can add to
one another;
• that is, they can
“summate.”This type
of summation is
called temporal
summation.

90. EPSP
• Summation
• Amplitude varies
• Dies off
• Ligand gated
channels
Action potential
• All or none law
• Fix amplitude
• Length of nerve fiber
• Voltage gated channels
• Shows absolute and
relative refractory
period

91. Electrical Events During Neuronal
Inhibition
Inhibitory post synaptic
potential
The inhibitory synapses
Open mainly chloride
channels,
An increase in negativity
beyond the normal
resting membrane
potential level is called
an inhibitory
postsynaptic potential
(IPSP)

92. TYPES OF INHIBITION
• Post synaptic
inhibition
• Presynaptic
inhibition

94. -Concepts of threshhold,
facilitation

95. SYNAPTIC FATIGUE
• When excitatory synapses are repetitively
stimulated at a rapid rate, the response by the
postsynaptic neuron is at first very great, but
the firing rate becomes progressively less in
succeeding milliseconds or seconds.
• This is called fatigue of synaptic transmission.
• The development of fatigue may be a
protective mechanism against excess neuronal
activity

96. The mechanism of fatigue is
mainly
• exhaustion or partial
exhaustion of the stores of
transmitter substance in
the presynaptic terminals.
• progressive inactivation of
many of the postsynaptic
membrane receptors
• slow development of
abnormal concentrations
of ions inside the
postsynaptic neuronal cell.

97. SYNAPTIC DELAY
During transmission of a neuronal signal from a
presynaptic neuron to a postsynaptic neuron, a
certain amount of time is consumed
• This is called the synaptic delay.
• Minimum delay time is 0.5 milliseconds
• From the measure of delay time, one can then
estimate the number of series neurons in the
circuit.

98. Reasons for synaptic delay
• discharge of the transmitter substance by the
presynaptic terminal,
• diffusion of the transmitter to the postsynaptic
neuronal membrane,
• action of the transmitter on the membrane
receptor,
• action of the receptor to increase the membrane
permeability, and
• inward diffusion of sodium to raise the excitatory
postsynaptic potential to a high enough level to
elicit an action potential.

99. Processing information and
memory
• The storage of information --- memory, is a function of
the synapses.
• Each time certain types of sensory signals pass through
sequences of synapses, these synapses become more
capable of transmitting the same type of signal the next
time, a process called facilitation.
• The synapses become so facilitated that signals
generated within the brain itself can also cause
transmission of impulses even when the sensory input is
not excited.
• This gives the person a perception of experiencing the
original sensations, although the perceptions are only
memories of the sensations.

100. Chemicals affecting neuronal
excitability
• Botulinium toxin prevents release of Ach by
binding VAMP
• Curare prevents interaction of Ach with its
receptors
• Tetrodotoxin blocks voltage gated Na channels
• Nerve gas inhibits acetylcholinesterase
• Neostigmine same
• Strychnine prevents IPSPs by blocking glycine
effect

101. Clinical
• Tetanus toxin
• Spastic paralysis by blocking presynaptic transmitter
(inhibitory) release in the CNS
• Botulinum toxins
• Causes flaccid paralysis by blocking the release of
acetylcholine at the NMJ
• The positive side!

102. phrospasm
Strabismus
Hemifacial spasm
Blocking Neurotransmitter release is useful treatment for:

103. Botox..

104. Drugs increasing neuronal
excitability
• Caffeine
• theophylline
• theobromine
found in coffee, tea, and cocoa, respectively,
all increase neuronal excitability, presumably by
reducing the threshold for excitation of
neurons.

105. Important neurotransmitters
• GABA
• Glycine
• Serotinin
• glutamate

106. Should know…
• Most common excitatory NT in CNS –
glutamate
• Most common inhibitory NT in CNS – glycine,
GABA
• NT can be inactivated via:
• Diffuses out of synaptic cleft
• Actively transported into pre-synp T
• Enzymatically degreaded (if the NT is acetycholine)

107. Summary
•A synapse is the anatomic site of electrical communication
betweens neurons or neurons and muscles or glands. It can
be Chemical or electrical
•Steps include Spread of AP in presynaptic membrane Ca
influx Nt release post synaptic receptors IPSP or EPSP
•G proteins act as intracellular second messengers; their
alpha and beta/gamma subunits triggering different
intracellular events
•Neurotransmitters maybe classified as Rapidly acting small
molecules or slowly acting neuropeptides/ growth factors