Neurophysiology explaining the synapses at nerve terminal and neuromuscular junctions and the various types of neurotransmitters found in blood that mediate the flow of electrical impulses in the central nervous system.
5. ANATOMICAL TYPES
Thursday, February 1, 2018
■ Axo-dendritic synapse
– between axon of one
to dendrite of other.
■ Axo-somatic – between
axon of one to
soma(body) of other.
■ Axo-axonic – between
two axons.
6. PHYSIOLOGICAL TYPES.
Thursday, February 1, 2018
■ Chemical – by
Neurotransmitter.(one
direction)
■ Electrical – transmission
through Gap junction.
(both direction)
■ Conjoint – Both chemical
& electrical transmission
co-exists.
8. STRUCTURE OF CHEMICAL SYNAPSE
Thursday, February 1, 2018
■ Synaptic knob or
button.
■ Pre synaptic
membrane.
■ Synaptic cleft.
■ Post synaptic process.
■ Post synaptic
membrane.
9. SYNAPTIC KNOB OR BUTTON.
Thursday, February 1, 2018
■
■
■
■
■
■
Axon loses myelin sheath.
End into small swellings as
knobs
Contains Mitochondria &
Neurotransmitters in vesicles
Circular – excitatory
Flat – inhibitory.
Transport –by Microtubules.
10. PRE SYNAPTIC MEMBRANE.
Thursday, February 1, 2018
■ Inner side contains
zone of dense
cytoplasm.
■ This forms
Presynaptic vesicular
grid.
12. POST SYNAPTIC PROCESS POST SYNAPTIC
MEMBRANE.
Thursday, February 1, 2018
■ Region of receiving
neuron.
■ Also contains zone of
dense cytoplasm.
■ Contains no of receptor
proteins projecting
outwards in cleft.
■ Neurotransmitter attaches
to these receptors.
13. RECEPTOR PROTEINS.
Thursday, February 1, 2018
■ Two types.
■ Ion channel receptor
proteins (Na, K, Cl)-
activation causes
opening of these
channels.
■ Enzymatic types of
receptor proteins –
■ Activation of cellular gene
■ Activation of protein
kinase.
14. TYPES OF CHEMICAL SYNAPSE
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Features Type I Type II
Structure Asymmetric Symmetric
Synaptic cleft Wider Narrower
Post synaptic
membrane thickening.
Marked Less marked
ECF in cleft Present Absent
Vesicle shape Spherical Flat
Neurotrasmitter. Ach, 5HT, Glutamate, E,
NE, DOPA, Adrenaline
GABA, Glycine
Effect Excitatory Inhibitory
Type of synapse. Axo-dendritic Axo-somatic.
15. PROCESS OF CHEMICAL SYNAPTIC
TRANSMISSION.
Thursday, February 1, 2018
■ Release of
Neurotransmitters.
■ Development of
EPSP & IPSP.
■ Removal of
Neurotransmitter
from synaptic cleft.
■ Development of
Action potential.
16. RELEASE OF
NEUROTRANSMITTERS.
Thursday, February 1, 2018
■ Nerve impulse reaches
nerve terminal
■ Depolarization of pre
synaptic membrane
■ voltage gated Ca channels
open
■ Ca permeability
■ Ca enters.
17. DEVELOPMENT OF EPSP.
■ EPSP – Depolarization
of post synaptic
membrane by
excitatory
neurotransmitter
(Glutamate)
■ Magnitude – 8mv
■ Latency – 0.5ms.
18. EPSP
Thursday, February 1, 2018
■ Ionic basis –
■ NT binds to receptors
proteins – opens ligand
gated Na & Ca channels
– Na diffuse in –
Depolarize membrane
■ Conduction of EPSP –
passively due to local
currents.
19. EPSP
.
■ Summation – EPSP is
graded response, does not
show all or none response
■ TEMPORAL – when
repeated stimuli applied in
short duration.
■ SPATIAL – when post
synaptic membrane
receives impulses
simulataneously from large
no of presynaptic terminals.
20. DEVELOPMENT OF IPSP.
Thursday, February 1, 2018
■ IPSP – Hyper polarization of
post synaptic membrane by
inhibitory neurotransmitter
(GABA)
■ Value of IPSP - -2mv
■ Summation.
■ Temporal
■ Spatial.
21. IPSP
Thursday, February 1, 2018
■ Ionic basis - Release of
inhibitory NT – open K or
Cl channels – diffusion of
K ions from neurons to
ECF or Cl from ECF into
neuron – Hyper
polarization
22. REMOVAL OF NEUROTRANSMITTER
FROM SYNAPTIC CLEFT.
Thursday, February 1, 2018
■ BY 3 WAYS.
■ Diffusion out of cleft.
■ Enzymatic
degradation –
acetylcholinesterase.
■ Active
neurotransmitter
reuptake.
23. DEVELOPMENT OF ACTION POTENTIAL.
Thursday, February 1, 2018
■ Synaptic integration
■ Generation of initial
segment spike.
■ Generation of
prolonged signals. i.
e Action Potential.
24. SYNAPTIC INTEGRATION
Thursday, February 1, 2018
■ It is phenomenon of
summation of both
EPSP or IPSP at the
post synaptic
membrane i.e
algebraically
summated potential
will determine
transmission.
25. GENERATION OF INITIAL SEGMENT SPIKE
Thursday, February 1, 2018
■ Summated potential 1st
pass to initial segment
i.e. axon hillock.
■ If potential is large
enough to depolarize
initial segment (6-10
mv) – initial spike is
generated
■ Magnitude – 30-40 mv.
26. GENERATION OF PROLONGED SIGNALS -- ACTION
POTENTIAL.
Thursday, February 1, 2018
■ Initial spike once
initiated causes further
depolarization by
opening voltage gated
Na channels on axon
hillock
■ Generate AP & travel
peripherally in axon.
28. POST-SYNAPTIC INHIBITION.
Thursday, February 1, 2018
■ Direct post synaptic
inhibition by
development of
inhibitory post synaptic
potential – by releasing
inhibitory NT.
■ Post synaptic inhibition
due to refractory period.
29. PRE-SYNAPTIC INHIBITION.
Thursday, February 1, 2018
■
■
■
By action of inhibitory
neuron (C) – releases
GABA
By opening Cl- channels of
pre synaptic terminals
produces hyperpolarization.
By activation of G protein.
■
■
By opening K+ channels
By directly blocking Ca
channels.
30. FEEDBACK INHIBITION
Renshaw cell inhibition.
Thursday, February 1, 2018
■ It occurs in spinal
alpha motor neuron
■ Neuron inhibits those
neuron which excite it.
■ It serves to limit
excitability of motor
neurons.
31. SIGNIFICANCE OF SYNAPTIC INHIBITION.
Thursday, February 1, 2018
■ Important for
restriction over
neurons & muscles to
react properly &
appropriately.
32. PROPERTIES OF SYNAPTIC
TRANSMISSION.
■ Facilitation.
■ Synaptic fatigue.
■ Synaptic plasticity &
learning.
■ Reverberation.
■ Reciprocal inhibition.
■ After discharge.
■ Effect of acidosis &
Hypoxia
■ One way conduction.
■ Synaptic delay.
■ Summation property of synapse.
■ Conversions & divergence.
■ Occlusion phenomenon.
■ Subliminal fringe effect.
33. ONE WAY CONDUCTION.
Thursday, February 1, 2018
■ Law of dynamic
polarity or Bell
Magendie law – synapse
allow only one way
conduction from pre to
post synaptic neuron.
■ Significance – For
orderly conduction of
impulse in one direction
only.
34. SYNAPTIC DELAY
Thursday, February 1, 2018
■ Time lapse between
arrival of nerve impulse
at the pre synaptic
terminal & its passage
to post synaptic
membrane.
■ 0.5 ms
35. CAUSES OF SYNAPTIC DELAY
Thursday, February 1, 2018
■ Release of
neurotransmitter.
■ Diffusion through
cleft
■ Binding with post
synaptic receptors &
opening ion channels.
■ Diffusion of ions
causing RMP.
36. SUMMATION PROPERTY OF SYNAPSE.
Thursday, February 1, 2018
■ Property of summation
is essential for
stimulation of post
synaptic membrane
either by stimulations
of large no of
Presynaptic terminals
or repeated
stimulation of single
terminal.
37. CONVERGENCE
Thursday, February 1, 2018
■ Phenomenon of
termination of signals
from many sources.
& DIVERGENCE.
■ One pre synaptic
neuron may terminate
on many post synaptic
neurons.
38. OCCLUSION PHENOMENON.
Thursday, February 1, 2018
■ Response to stimulation
of 2 pre synaptic
neurons is less than sum
total of the response
obtained when
stimulated seperately.
39. FACILITATION.
Thursday, February 1, 2018
■ When pre synaptic axon
is stimulated with
several consecutive
individual stimuli, each
evokes larger post
synaptic potential than
previous stimuli.
■ Cause – Prolonged Ca
channel opening.
40. SYNAPTIC FATIGUE.
Thursday, February 1, 2018
■ Pre synaptic neuron
when stimulated
continuously there is
Gradual Decrease &
finally disappearance of
post synaptic response.
■ Cause –
■ Gradual inactivation of
Ca
■ Accumulation of waste.
41. SYNAPTIC PLASTICITY & LEARNING.
Thursday, February 1, 2018
■ Synaptic transmission
can be increased or
decreased on the basis of
past experience
■ Post tetanic potentiation.
■ Long term potentiation
■ Sensitization
■ Long term depression.
42. REVERBERATION.
Thursday, February 1, 2018
■ Passage of impulse
from pre synaptic
neuron and again
back to presynaptic
neuron to cause
continuous
stimulation of Pre
synaptic Neuron.
43. RECIPROCAL INHIBITION.
Thursday, February 1, 2018
■ Afferent signal
activates excitatory
neurons to group of
muscles &
simultaneously
inhibitory neurons to
antagonistic muscles.
47. Objectives
• Explain how a single neurotransmitter may be excitatory at one
synapse and inhibitory at another.
• Describe the structural and functional properties of the major classes
of neurotransmitters.
• Describe the most common excitatory and inhibitory
neurotransmitters in the CNS.
48. Neurotransmitters
• They all exhibit the following effects:
• They are made in either the cell body or the axon terminal and
packaged into synaptic vesicles,
• they are released from the presynaptic neuron, they bind to their
receptors on the postsynaptic membrane, and
• finally their effects are often rapidly terminated through removal
and/or degradation
49. Nearly all neurotransmitters induce postsynaptic potentials by binding
to their receptors in the postsynaptic membrane. The type of receptor
to which a neurotransmitter binds determines the postsynaptic
response. Two types of neurotransmitter receptors have been
identified: ionotropic and metabotropic.
Ionotropic receptors
Metabotropic Receptors
50. Ionotropic
Receptors
• These are receptors that are part of
ligand-gated ion channels.
• They are called ionotropic because
they directly control the movement
of ions into or out of the neuron
when bound by a neurotransmitter.
• Neurotransmitters that bind
ionotropic receptors have very rapid
but short-lived effects on the
membrane potential of the
postsynaptic neuron.
51. Metabotropic
Receptors
• are receptors within the plasma membrane
that are connected to a separate ion
channel in some fashion.
• They are called metabotropic because they
are directly connected to metabolic
processes that begin when they are bound
by neurotransmitters.
• Most are connected through a group of
intracellular enzymes called G-proteins.
When the neurotransmitter molecule binds
to the receptor, it activates one or more G-
proteins and begins a cascade of enzyme-
catalyzed reactions that ends in the
formation of a molecule inside the
postsynaptic neuron, called a second
messenger
52. Metabotropic
receptors
• The second messenger then opens or closes an ion
channel in the plasma membrane of the
postsynaptic neuron.
• The changes that metabotropic receptors elicit in
the membrane potential of the postsynaptic neuron
occur much more slowly,but are typically longer-
lasting and more varied than those of ionotropic
receptors.
• An example of a common second messenger is the
molecule cyclic adenosine monophosphate (or
cAMP), which is derived from ATP. In the neuron,
cAMP has multiple functions, including binding a
group of enzymes that add phosphate groups to ion
channels, triggering them to open or close.
53. CRITERIA FOR
NEUROTRANSMITTER.
• Should be synthesized by pre synaptic neuron & stored in vesicle.
• Should be released by stimulation of nerve.
• Travels a short distance of synaptic cleft.
• Associated with enzyme or enzyme system for
• inactivation.
• When applied extrinsically should mimic effect of nerve stimulation.
• Regardless of the type of receptor that a neurotransmitter binds,
that binding leads to either EPSPs or IPSPs.
• Neurotransmitters that induce EPSPs in the postsynaptic neuron are
said to have excitatory effects; those that induce IPSPs have
inhibitory effects.
• A single neurotransmitter can have both inhibitory and excitatory
effects depending on which neurotransmitter it binds on the post
synaptic neuron.
54. CLASSIFICATION.
■ Neurotransmitters operating within the nervous system are
usually classified into four groups by their chemical structures.
■ Biochemical
■ Small molecule
■
■
■ Acetylcholine
Biogenic amines. (E,NE, DA,5HT, Histamine)
Amino acids (GABA, Glycine, Glutamate,
Aspartate)
■ Neuro peptide.
■ Physiological
■ Excitatory
■ Inbitory
55. ACETYLCHOLINE
Thursday, February 1, 2018
■ Principal NT released by cholinergic neurons.
■ At N-M junction.
■ Preganglionic & post-ganglionic Para-
sympathetic
■ Preganglionic Sympathetic.
■ Postganglionic sympathetic which innervates –
sweat glands & skeletal muscle blood vessels.
■ Ending of Amacrine cells of retina.
56. ACETYLCHOLINE
■ Receptors – Nicotinic &
Muscarinic.
■ Synthesis & storage – in
Mitochandria by AchCoa &
stored in vesicles.
■ Actions – most places its
excitatory but few (vagus
supplying heart) – inhibitory.
57. MUSCARINIC VERSUS NICOTINIC ACTIONS OF AcH.
FEATURES MUSCARINIC NICOTINIC
Site of action Post synaptic in Cardiac ❖All Autonomic
muscle, Smooth muscle Ganglia
& Glandular cells. ❖N-M junction in
skeletal muscles.
Characteristics of action ❖Same as Mushroom ❖Same as drug
poison – Muscarine. Nicotine.
❖Action – slow in onset. ❖Action – Quick in
❖Duration - Prolonged. onset.
❖Duration – Brief.
Actions antagonised by Atropine ❖Hexamethonium at
Autonomic Ganglia
❖Tubocurarine at
skeletal muscles.
58. BIOGENIC AMINES.
■ Catecholamines.
■ Epinephrine – mainly from
adrenal medulla.
■ Nor-epinephrine –
■ Post Ganglionic Symp
■ Cerebral cortex &
Hypothalamus.
■ Pons & Medulla.
Thursday, February 1, 2018
■ Synthesis of
catecholamine.
59. Dopamine.
• Dopamine, used extensively in the CNS, has a variety of functions.
• It helps to coordinate movement, and is also involved in emotion and
motivation.
• The receptor for dopamine in the brain is a target for certain illegal
drugs, such as cocaine and amphetamine, and is likely responsible for
the behavioral changes seen with addiction to these drugs.
60. DOPAMINE
■ Naturally acting
precursors of NE.
■ Receptors
■
■
■ D1 – Activates adenyl cyclase
via Gs protein
D2 – Inhibit adenyl cyclase
via Gi protein.
D3 – Localised to Nucleus
Accumbens.
■ Neurons – in Mid brain
to
■ Striatum
■ Olfactory tubercle
■ Nucleus accumbens
■ limbic system area.
■ Highest conc present in
Basal Ganglia, limbic
system & CTZ in medulla.
61. FUNCTIONAL ROLES OF DOPAMINE
■ Control of Movements
■ Induction of Vomiting.
■ Inhibition of Prolactin secretion & stimulation of
GnRH.
■ Retina – Inhibitory Neurons.
■ Schizophrenia type of Psychosis due to Increased
levels of D2 receptors.
62. SEROTONIN.
Thursday, February 1, 2018
■ Synthesis – from
Tryptophan.
■ Metabolism –
Inactivated by MAO to
5-hydroxy indole acetic
acid(5-HIAA)
■ Sites of secretion
■ In Brain
■ Non-neural cells.
63. SEROTONIN.
Thursday, February 1, 2018
■ Serotonin receptors –
■ 7 group of receptors
(5HT1-5HT7) with further
groups A-F.
■ Functional role in CNS
■ Regulation of carbohydrate
intake & Hypothalamic
releasing hormones.
■ Pain inhibition.
■ Hallucination
64. HISTAMINE
■ Sites of secretion
■ In Brain & Non-neural cells.
■ Histamine receptors
■ H1 – activates Phospholipase C
■ H2 – increases intracellular cAMP
■ H3 – inhibition of histamine via G protein.
■ Functional role
■ Excitatory
■ Arousal & sexual behaviour, Regulation of ant pituitary, Drinking, Pain
threshold & Itch sensation.
65. AMINO ACID
NEUROTRANSMITTERS
• Glutamate; glycine; and g-aminobutyric
acid, or GABA.
• Glutamate is the most important
excitatory neurotransmitter in the CNS—
it is estimated that over half of all
synapses in the CNS release glutamate.
• When it binds to its ionotropic
postsynaptic receptors, glutamate
triggers the opening of a type of channel
that can pass both sodium and calcium
ions.
• This elicits an EPSP in the postsynaptic
neuron.
■ Excitatory
■ Glutamate – Brain &
dorsal sensory nerve
■ Aspartate - Cortical
pyramidal cells.
■ Inhibitory
■ GABA – whole CNS
■ Glycine. – Grey matter of
spinal cord & brain stem.
66. GLUTAMIC ACID
■ Synthesis – Mainly
from Glucose via Kreb
cycle or Glutamine,
synthesized by Glial
cells & taken by
neurons.
■ Receptors – High
conc in Hippocampus
& Cerebellum.
67. GABA &
Glycine
• Receptors –
• A – Inhibition by increasing Cl conductance
• B – By K conductance
• C – in Retina.
• Glycine and GABA are the two major inhibitory
neurotransmitters of the nervous system. Both induce IPSPs in
the postsynaptic neurons primarily by opening chloride ion
channels and hyperpolarizing the axolemma. GABA use is
widespread in the CNS; as many as one-third of neurons in the
brain use it as their major inhibitory neurotransmitter. Glycine is
found in about half of the inhibitory synapses in the spinal cord;
the remainder of the synapses use GABA.
68. NEUROPEPTIDE
TRANSMITTERS.
• Mechanism of action –
• Alter ion channel function, modify cell metabolism & gene
expression.
• Types.
• Neuroactive peptides – TRH, LH releasing hormone,
somatostatin.
• Pituitary peptides – Vasopressin & Oxytocin.
• Peptides acting on the Gut and Brain – Leucine,
Enkephalin, Methionine, Sub P, Cholecystokinin, VIP,
Neurotensin, Insulin, Glucose, Opioid polypeptides.
Thursday, February 1, 2018
69. Apply What you learned
• Which neurotransmitters have largely excitatory effects?
• Which neurotransmitters have largely inhibitory effects?
• . Predict the effects of the poison strychnine, which blocks glycine
receptors on postsynaptic neurons of the CNS.
Think About it??
