SYNAPSE

DR NILESH KATE
MBBS,MD
ASSOCIATE PROF
ESIC MEDICAL COLLEGE, GULBARGA.
DEPT. OF PHYSIOLOGY
 OBJECTIVES
 SYNAPSE
 Types
 CHEMICAL SYNAPSE
 Structure
 Process
 Inhibition
 properties
 NEUROTRANSMITTERS.
 APPLIED.
 SYNAPSE
 Definition – Synapse
is the functional
communicating
junction between 2
nerve cells.

Thursday, February 1, 2018

 TYPES

 Anatomical types

 Physiological types.

Thursday, February 1, 2018

 ANATOMICAL TYPES
 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.

Thursday, February 1, 2018

 PHYSIOLOGICAL TYPES.
 Chemical – by
Neurotransmitter.(one
direction)
 Electrical – transmission
through Gap junction.
(both direction)
 Conjoint – Both chemical
& electrical transmission
co-exists.

Thursday, February 1, 2018

 CHEMICAL SYNAPSE
 Structure
 Process
 Inhibition
 Properties

Thursday, February 1, 2018

 STRUCTURE OF CHEMICAL
SYNAPSE
 Synaptic knob or
button.
 Pre synaptic
membrane.
 Synaptic cleft.
 Post synaptic process.
 Post synaptic
membrane.

Thursday, February 1, 2018

 SYNAPTIC KNOB OR BUTTON.
 Axon loses myelin sheath.
 End into small swellings as
knobs
 Contains Mitochondria &
Neurotransmitters in vesicles
 Circular – excitatory
 Flat – inhibitory.
 Transport –by Microtubules.

Thursday, February 1, 2018

 PRE SYNAPTIC MEMBRANE.
 Inner side contains
zone of dense
cytoplasm.
 This forms
Presynaptic vesicular
grid.

Thursday, February 1, 2018

 SYNAPTIC CLEFT.
 Gap between pre &
post.
 20-40 nm wide.
 Contains ECF with
Glycoproteins.

Thursday, February 1, 2018

 POST SYNAPTIC PROCESS
POST SYNAPTIC MEMBRANE.
 Region of receiving
neuron.
 Also contains zone of
dense cytoplasm.
 Contains no of receptor
proteins projecting
outwards in cleft.
 Neurotransmitter attaches
to these receptors.

Thursday, February 1, 2018

 RECEPTOR PROTEINS.
 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.

Thursday, February 1, 2018

 TYPES OF CHEMICAL SYNAPSE
Features Type I Type II
Structure Asymmetric Symmetric
Synaptic cleft Wider Narrower
Post synaptic Marked Less marked
membrane thickening.
ECF in cleft Present Absent
Vesicle shape Spherical Flat
Neurotrasmitter. Ach, 5HT, Glutamate, E, GABA, Glycine
NE, DOPA, Adrenaline
Effect Excitatory Inhibitory
Type of synapse. Axo-dendritic Axo-somatic.

Thursday, February 1, 2018

 PROCESS OF CHEMICAL
SYNAPTIC TRANSMISSION.
 Release of
Neurotransmitters.
 Development of
EPSP & IPSP.
 Removal of
Neurotransmitter
from synaptic cleft.
 Development of
Action potential.

Thursday, February 1, 2018

 RELEASE OF
NEUROTRANSMITTERS.
 Nerve impulse reaches
nerve terminal
 Depolarization of pre
synaptic membrane
 voltage gated Ca channels
open
 Ca permeability
 Ca enters.

Thursday, February 1, 2018

 Dale’s Phenomenon.
 Ca levels in axon
 Exocytosis of vesicles
releasing
neurotransmitter into
cleft.
 Kiss and Run
discharge of NT
 1st Propounded by
Dale.

Thursday, February 1, 2018

 DEVELOPMENT OF EPSP.
 EPSP – Depolarization
of post synaptic
membrane by
excitatory
neurotransmitter
(Glutamate)
 Magnitude – 8mv
 Latency – 0.5ms.

Thursday, February 1, 2018

 EPSP
 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.

Thursday, February 1, 2018

 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.

Thursday, February 1, 2018

 DEVELOPMENT OF IPSP.
 IPSP – Hyper polarization of
post synaptic membrane by
inhibitory neurotransmitter
(GABA)
 Value of IPSP - -2mv
 Summation.
 Temporal
 Spatial.

Thursday, February 1, 2018

 IPSP
 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

Thursday, February 1, 2018

 REMOVAL OF NEUROTRANSMITTER
FROM SYNAPTIC CLEFT.
 BY 3 WAYS.
 Diffusion out of cleft.
 Enzymatic
degradation –
acetylcholinesterase.
 Active
neurotransmitter
reuptake.

Thursday, February 1, 2018

 DEVELOPMENT OF ACTION
POTENTIAL.
 Synaptic integration
 Generation of initial
segment spike.
 Generation of
prolonged signals. i.
e Action Potential.

Thursday, February 1, 2018

 SYNAPTIC INTEGRATION
 It is phenomenon of
summation of both
EPSP or IPSP at the
post synaptic
membrane i.e
algebraically
summated potential
will determine
transmission.

Thursday, February 1, 2018

 GENERATION OF INITIAL
SEGMENT SPIKE.
 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.

Thursday, February 1, 2018

 GENERATION OF PROLONGED
SIGNALS -- ACTION POTENTIAL.
 Initial spike once
initiated causes further
depolarization by
opening voltage gated
Na channels on axon
hillock
 Generate AP & travel
peripherally in axon.

Thursday, February 1, 2018

 INHIBITION AT SYNAPSES
 Post-synaptic
inhibition.
 Pre-synaptic
inhibition.
 Feedback inhibition.
 Feed forward
inhibition.

Thursday, February 1, 2018

 POST-SYNAPTIC INHIBITION.
 Direct post synaptic
inhibition by
development of
inhibitory post synaptic
potential – by releasing
inhibitory NT.
 Post synaptic inhibition
due to refractory period.

Thursday, February 1, 2018

 PRE-SYNAPTIC INHIBITION.
 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.

Thursday, February 1, 2018

 FEEDBACK INHIBITION
Renshaw cell inhibition.
 It occurs in spinal
alpha motor neuron
 Neuron inhibits those
neuron which excite it.
 It serves to limit
excitability of motor
neurons.

Thursday, February 1, 2018

 FEED FORWARD INHIBITION.
 A neuron is connected
through 2 pathways,
excitatory &
inhibitory.
 It allows brief &
precisely timed
excitation.

Thursday, February 1, 2018

 SIGNIFICANCE OF SYNAPTIC
INHIBITION.
 Important for
restriction over
neurons & muscles to
react properly &
appropriately.

Thursday, February 1, 2018

 PROPERTIES OF SYNAPTIC
TRANSMISSION.
 One way conduction.
 Synaptic delay.
 Summation property of
synapse.
 Conversions &
divergence.
 Occlusion phenomenon.
 Subliminal fringe effect.
Thursday, February 1, 2018
 Facilitation.
 Synaptic fatigue.
 Synaptic plasticity &
learning.
 Reverberation.
 Reciprocal inhibition.
 After discharge.
 Effect of acidosis &
Hypoxia
 ONE WAY CONDUCTION.
 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.
Thursday, February 1, 2018
 SYNAPTIC DELAY
 Time lapse between
arrival of nerve impulse
at the pre synaptic
terminal & its passage
to post synaptic
membrane.
 0.5 ms

Thursday, February 1, 2018

 CAUSES OF SYNAPTIC DELAY
 Release of
neurotransmitter.
 Diffusion through
cleft
 Binding with post
synaptic receptors &
opening ion channels.
 Diffusion of ions
causing RMP.

Thursday, February 1, 2018

 SUMMATION PROPERTY OF
SYNAPSE.
 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.
Thursday, February 1, 2018
CONVERGENCE & DIVERGENCE.
 Phenomenon of  One pre synaptic
termination of signals neuron may terminate
from many sources. on many post synaptic
neurons.

Thursday, February 1, 2018

 OCCLUSION PHENOMENON.
 Response to stimulation
of 2 pre synaptic
neurons is less than sum
total of the response
obtained when
stimulated seperately.

Thursday, February 1, 2018

 SUBLIMINAL FRINGE EFFECT.

Thursday, February 1, 2018

 FACILITATION.
 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.

Thursday, February 1, 2018

 SYNAPTIC FATIGUE.
 Pre synaptic neuron
when stimulated
continuously there is
Gradual Decrease &
finally disappearance of
post synaptic response.
 Cause –
 Gradual inactivation of
Ca
 Accumulation of waste.

Thursday, February 1, 2018

 SYNAPTIC PLASTICITY &
LEARNING.
 Synaptic transmission
can be increased or
decreased on the basis of
past experience
 Post tetanic potentiation.
 Long term potentiation
 Sensitization
 Long term depression.

Thursday, February 1, 2018

 REVERBERATION.
 Passage of impulse
from pre synaptic
neuron and again
back to presynaptic
neuron to cause
continuous
stimulation of Pre
synaptic Neuron.

Thursday, February 1, 2018

 RECIPROCAL INHIBITION.
 Afferent signal
activates excitatory
neurons to group of
muscles &
simultaneously
inhibitory neurons to
antagonistic muscles.

Thursday, February 1, 2018

 AFTER DISCHARGE.
 Single instantaneous
input results into
sustained output
signals.

Thursday, February 1, 2018

 EFFECT OF ACIDOSIS &
HYPOXIA
 Synaptic transmission
is vulnerable to
acidosis & Hypoxia.

Thursday, February 1, 2018

 NEUROTRANSMITTERS.
 Def – Chemical substances
responsible for
transmission of impulse
through synapse.

Thursday, February 1, 2018

 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.

Thursday, February 1, 2018

 CLASSIFICATION.
 Biochemical
 Small molecule
 Acetylcholine
 Biogenic amines. (E,NE, DA,5HT, Histamine)
 Amino acids (GABA, Glycine, Glutamate, Aspartate)
 Neuro peptide.
 Physiological
 Excitatory
 Inbitory

Thursday, February 1, 2018

 ACETYLCHOLINE
 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.

Thursday, February 1, 2018

 ACETYLCHOLINE
 Receptors – Nicotinic &
Muscarinic.
 Synthesis & storage – in
Mitochandria by AchCoa
& stored in vesicles.
 Actions – most places its
excitatory but few (vagus
supplying heart) –
inhibitory.

Thursday, February 1, 2018

 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.
Thursday, February 1, 2018
 BIOGENIC AMINES.
 Catecholamines.  Synthesis of
 Epinephrine – mainly catecholamine.
from adrenal medulla.
 Nor-epinephrine –
 Post Ganglionic Symp
 Cerebral cortex &
Hypothalamus.
 Pons & Medulla.

Thursday, February 1, 2018

 Phenylalanine

Thursday, February 1, 2018

 DOPAMINE
 Naturally acting  Neurons – in Mid brain
precursors of NE. to
 Receptors  Striatum
 D1 – Activates adenyl cyclase  Olfactory tubercle
via Gs protein  Nucleus accumbens
 D2 – Inhibit adenyl cyclase
via Gi protein.  limbic system area.
 D3 – Localised to Nucleus  Highest conc present in
Accumbens.
Basal Ganglia, limbic
system & CTZ in medulla.

Thursday, February 1, 2018

 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.

Thursday, February 1, 2018

 SEROTONIN.
 Synthesis – from
Tryptophan.
 Metabolism –
Inactivated by MAO to
5-hydroxy indole acetic
acid(5-HIAA)
 Sites of secretion
 In Brain
 Non-neural cells.

Thursday, February 1, 2018

 SEROTONIN.
 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
Thursday, February 1, 2018
 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.
Thursday, February 1, 2018
 SYNTHESIS & CATABOLISM OF
HISTAMINE.

Thursday, February 1, 2018

 AMINO ACID
NEUROTRANSMITTERS
 Excitatory
 Glutamate – Brain &
dorsal sensory nerve
 Aspartate - Cortical
pyramidal cells.
 Inhibitory
 GABA – whole CNS
 Glycine. – Grey matter of
spinal cord & brain stem.

Thursday, February 1, 2018

 GLUTAMIC ACID
 Synthesis – Mainly
from Glucose via Kreb
cycle or Glutamine,
synthesized by Glial
cells & taken by
neurons.
 Receptors – High
conc in Hippocampus
& Cerebellum.

Thursday, February 1, 2018

 GABA
 Receptors –  Formation of GABA.
 A – Inhibition by
increasing Cl
conductance
 B – By K conductance
 C – in Retina.

Thursday, February 1, 2018

 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

THANK YOU