Synapse by sunita tiwale

Synapse
By
Dr Sunita Tiwale
Professor, Dept of Physiology
D.Y.Patil Medical College Kolhapur

Synapse
Sherrington
Site of contiguity (Contact without continuity)

www.sanger.ac.uk/.../gfx/070305_synapse_300.jpg

• Synapse – Greek word –synaptein. Syn –together;
aptein –clasp.
• Synapse – Clasping of hands (as in hand shaking
between two friends).
• Site of functional continuity (transneuronal
junctional complex) between two neurons.
• Why need of synapse?
• Function- Transmit impulse from one neuron to
another.
• Importance - Permit grading & modulation of
neural activities.
• Synaptic mechanism is a sort of resistance in the
pathway of the impulse to have variable responses
from the effector organ depending on the nature &
intensity of the stimulus.

• Definition: Specialized anatomical junction
between two neurons, where electrical activity of
one neuron i.e. (presynaptic neuron) influences the
electrical or metabolic activity of other neuron
(postsynaptic neuron) without structural continuity.

Classification of Synapse:
I)Anatomical/Histological:
a) Axodendritic: Most commonly seen.
Site: In cerebellum – Climbing fibres,
In cerebrum 98% – Apical dendrites of
cortical pyramidal cells.
Spinal cord: Motor neurons
b) Axosomatic :
Site : Spinal cord :Motor neuron.
Cerebellum : Basket cells with Purkinje cells.
Autonomic ganglia, 2% in cerebral cortex
c) Axoaxonal : Site: Spinal cord
d)Dendrodendritic: Rare.
Site : Olfactory bulb : Synapse between mitral &
granule cells.

II) PHYSIOLOGICAL CLASSIFICATION OF SYNAPSES:
Physiological/
functional
Classification
Chemical
synapse
Electrical
synapse
Mixed /Conjoint
synapse
Depending on type of transmission

• Chemical Synapse: Transmission is through chemical
messengers i.e. Neurotransmitters. Site: CNS in
human.
• Action potentials cannot cross the synaptic cleft
present between 2 neurons.
• Nerve impulse is carried by neurotransmitters which
transmit the nerve impulse from one nerve cell to the
next across the synapse.
• Impulse in the axon terminal of Presynaptic neuron
causes release of neurotransmitters like Acetylcholine
or Serotonin by exocytosis & diffuses in the synaptic
cleft (larger than electrical synapse).

• This chemical mediator binds to receptors on the
surface of the Postsynaptic neuron.
• This triggers events that open or close channels in
the membrane of the postsynaptic cell.
• Advantage : Thus excites, inhibits or modifies the
sensitivity of the postsynaptic neuron (unique
feature of this synapse).
• Signal transmission unidirectional, requires energy
so active process.
• Speed of signal transmission :At moderate speed.

Electrical Synapse :
• Membrane of Presynaptic & Postsynaptic neurons
come together to form Gap junction between the two
cells, like the intercellular junctions in other tissues.
• They form low resistance bridges through which ions
pass with relative ease (signal transmission in the
form of electrical signals).
• Gap junctions of only 2-3 nm (space is very small) .
• Cytoplasmic continuity present.
• No synaptic delay. Signal transmission very fast.
• Bidirectional conduction.

• No energy consumption during signal
transmission. So passive process.
• Disadvantage : Signals not modified (no gain,
signals remain same or reduced as compared to
originating neurons).
• These synapses occur in mammals & there is
electrical coupling.
• e.g – some of the neurons in the lateral Vestibular
nucleus.

3. Conjoint/Mixed Synapse :
• Having both electrical & chemical transmission,
exists within the same networks of inhibitory cells.
• Chemical & electrical synapses perform
complementary roles.
• Why chemical synapses?
• Chemical synapses are slower than electrical
synapses, so why does our body rely on them?
• chemical signal can be fine tuned. Neurons can
interact to inhibit themselves or other neurons to
increase the resolution of a signal.

Functional anatomy of Synapse :
Each neuron divides to form 2000 synaptic endings.
10 11 Neurons in human CNS so 2 x 1014 synapses.
Presynaptic neuron—conducts impulses toward the
synapse (sending side)
Postsynaptic neuron—transmits impulses away from
the synapse (receiving side).
SYNAPSE= Presynaptic terminal + Synaptic cleft +
Postsynaptic membrane

General features at the zone of synapse :
1) Presynaptic terminal: Terminal branch of the axon
(presynaptic neuron) enlarges – presynaptic knobs,
terminal knobs, boutons or end feet.
Presynaptic terminal/knob: a) cell membrane –
Presynaptic membrane,
Two internal structures : b) Synaptic/Transmitter
vesicles & c) Mitochondria.
Synaptic vesicles have a v – snare protein in their walls
synaptobrevin which locks with the t – snare protein
syntaxin in the Presynaptic cell membrane.
Structure of Synapse

• Transmitter/synaptic vesicles contain
neurotransmitters.
Three types of synaptic vesicles:
a) Small clear synaptic vesicles –Ach, glycine, GABA
or glutamate.
b) Small vesicles with dense core – catecholamines.
c) Large vesicles with dense core – neuropeptides.
• Vesicles & proteins in their walls synthesized in
golgi apparatus of neuronal cell body, migrate
down the axon to the terminal by axoplasmic
transport.
• Mitochondria provide ATP for synthesis of
neurotransmitter

• Small molecule neurotransmitters are synthesized
& packed into synaptic vesicles in the axon
(presynaptic) terminal.
• Neuropeptides synthesized by nerve cell body,
packed into vesicles in golgi apparatus, these
vesicles are delivered to axon terminal.
• Pre synaptic membrane –thickened at the synaptic
cleft called as active zones which contain many
proteins & row of Ca++ channels.
• Ca++ is the key to synaptic vesicle fusion with cell
membrane & discharge of neurotransmitter.

• An action potential reaching presynaptic terminal
opens voltage- gated Ca++ channels & the resulting
Ca++ influx triggers release of neurotransmitters.
• Ca content restored back to resting level by rapid
sequestration & removal from the cell primarily by
Ca Na antiport.
• Vesicles fuse with the membrane (Synaptobrevin
fuses with syntaxin), discharge the transmitter into
synaptic cleft by exocytosis.
• Vesicles retrieved by endocytosis. They enter
endosomes, budded off & refilled, starting the cycle
over again.

• Thus small clear vesicles & small dense core
vesicles recycle in the end.
• Tetanus toxin acts on synaptobrevin also
botulinium toxins B, D, F & G blocks presynaptic
transmitter release causing spastic paralysis.
• Botulism blocks release of Ach at neuromuscular
junction causing flaccid paralysis.
• Botulism toxin has proved effective in the
treatment of muscle hyperactivity e.g to relieve
achalasia & injection into facial muscles to remove
wrinkles.

2) Synaptic cleft :
• Gap of 20 nm width exists between pre &
postsynaptic membranes.
• Filled with extracellular fluid.
• Neurotransmitter is released from the
presynaptic membrane into synaptic cleft.
• Enzymes are present in the cleft to destroy
neurotransmitter after its action on post
synaptic membrane is over.

3)Post synaptic membrane:
• Thickened across the synaptic cleft –Subsynaptic
membrane/post synaptic density.
• It has specific receptor binding proteins & enzymes.
• Receptors – Two components:
1) A binding component - protrudes outwards
into the synaptic cleft & binds with neurotransmitter
released from presynaptic terminal.
2) An ionophore component – occupy whole
thickness of post synaptic membrane &
protrudes inside the post synaptic neurone.

• Ionophore two types –
a)An ion channel – Allows passage of specified
types of ions.
b) A second messenger activator – Protrudes into
the cell cytoplasm & activates one or more
substances inside the post synaptic neurone.
• These substances in turn acts as second
messengers to change specific internal cellular
functions.
• Ion channels two types:
1)Cation channel : Allows Na to pass, sometimes K
or Ca.
2) Anion channel : Allow Cl to pass also minute
quantities of other anions.

• Neurotransmitter substances that open Cation
channel – excitatory transmitter (Na excites post
synaptic neuron).
• Transmitter substances that open anion channel –
inhibitory transmitter (allow –ve electrical charges
to enter which inhibits post synaptic neuron).
• Opening & closing of channels occurs within
fraction of a millisecond, thus provide a means for
rapid control of post synaptic neurons.

Second messenger system in the Postsynaptic neuron:
• The process of memory- require prolonged changes in
neurons.
• Achieved by activating a second messenger chemical
system inside the post synaptic neuronal cell itself.
• Most prevailing type in neurons is the G protein.
• G protein – attached to the inner portion of
Membrane receptor protein.
• 3 components of G protein : alpha, beta & gamma.
• Alpha component separates on activation & performs
one or multiple function.

Changes which occur are :
1) Opening specific ion channels through the post
synaptic membrane, e.g K+ channel remains
open for prolonged time.
2) Activation of cAMP & cGMP: Initiate long term
changes in cell structure itself → alters long
term excitability of neurons
3) Activation of one or more intracellular enzymes →
cause any one of many specific chemical
functions in the cell.
4) Activation of Gene transcription: Most important.
Formation of new proteins within the neurons
→ Can change metabolic machinery of the cell
or its structure. Occurs in long term memory
process.

• Thus post synaptic receptors after activation either
cause excitation or inhibition.
• Importance of both types of receptors is that it allows
restrain as well as excitation which gives additional
dimension to nervous function.
• Excitation occurs by :
1)Opening of Na channels → Na influx →positivity
inside the cell toward the threshold level for excitation.
Most widely used means of excitation.
• 2) Depressed conduction through Cl or K channels.
• 3) Various change in the internal metabolism of the
cell – a)To excite cell activity or
b) To ↑ the number of excitatory membrane
receptors or
c) to ↓ number of inhibitory membrane
receptor.

• Inhibition occurs by
1) Opening of Cl ion channels through receptor.
2) ↑ in conductance of K ion through receptor.
3) Activation of receptor enzymes that
a) inhibit cellular metabolic function or
b)↑the number of inhibitory synaptic
receptors or
c) to ↓ number of excitatory membrane
receptors.
• More than 50 synaptic transmitters have been
found: Two types:
• 1) Small molecules rapidly acting →acute
responses of the nervous system like transmission
of sensory signals to brain & motor signals back to
muscles.

2) Neuropeptides – large molecular size – slow
acting-more potent –prolonged action such as long
term changes in:
• Numbers of neuronal receptors,
• Opening or closure of certain ion channels
• Numbers of synapses
• Sizes of synapses
e.g – Hypothalamus releasing hormones-TRH,
GnRH, Somatostatin, Pituitary peptides –LH, TSH,
Growth hormone, ADH, Oxytocin, GIT peptides.

Functional Classification of Neurotransmitters
• Excitatory (depolarizing) and inhibitory
(hyperpolarizing).
• Determined by receptor type on postsynaptic
neuron
• GABA usually inhibitory
• Glutamate, epinephrine usually excitatory
• Acetylcholine
• Excitatory at neuromuscular junctions in skeletal
muscle
• Inhibitory in cardiac muscle

Synaptic Transmission: Mechanism Of
Conduction of an Impulse in a chemical
synapse
Sequence of events :
1)Release of neurotransmitter
2)Development of Excitatory or Inhibitory
postsynaptic potential
3)Removal of neurotransmitter from synaptic cleft
4)Development of action potential

Release of neurotransmitter:
Action potential in the axon reaches the presynaptic
terminal resulting in depolarization of presynaptic
terminal
↓
voltage-gated Ca2+ channels on the presynaptic
membrane open
↓
influx of Ca2+ from ECF of the synaptic cleft into
presynaptic terminal. This stimulates sliding of synaptic
vesicles towards presynaptic membrane
↓
synaptic vesicles fuse with the pre-synaptic membrane
by exocytosis of vesicles
↓
neurotransmitter released into synaptic cleft, diffuses
across synaptic cleft and binds to the receptors on the
post-synaptic membrane

Single action potential from the Presynaptic terminal
does not lead to the formation of propagated action
potential in the Postsynaptic neuron but it produces
either a transient partial depolarization (opening of
Na channels) or a transient hyperpolarization (opening
of K channels) → Graded potential.
Graded potentials strength determined by:
Amount of neurotransmitter released (it depends on
Ca influx).
Time the neurotransmitter is in the synaptic cleft.
Development of Electrical events at the Synapses

Two Types of Events:
1)Excitatory postsynaptic potentials (EPSP)
2)Inhibitory postsynaptic potentials (IPSP)
Special features of Soma of the neuron :
• RMP of neuronal soma is less negative (-65mv) as
compared to peripheral nerves (-90mv).
• Advantage : Neuron can function in two ways.
• If RMP becomes less –ve the postsynaptic membrane
becomes more excitable.
•If RMP becomes more –ve the postsynaptic
membrane becomes less excitable.
• Neuron can function in two modes –excitation or
inhibition.

2) Interior of neuronal soma contains
a)highly conductive electrolyte solution (ICF).
b)Diameter of neuronal soma larger (10 to 80 µm).
Advantage :
i)Almost no resistance to conduction of electric current
from one part of somal interior to another part.
ii) So any change in potential in any part of intra somal
fluid causes an almost exactly equal change in
potential at all points inside the soma.
Feature plays important role in the summation of signals
entering the neuron from multiple sources.

Excitatory postsynaptic potentials (EPSP) :
Presynaptic terminal →Release of neurotransmitter →
Binds with receptors of postsynaptic membrane →
partial depolarization of postsynaptic membrane.
This partial depolarizing response begins after 0.5msec
of entering of afferent impulse into spinal cord.
Reaches a peak after 1 -1.5msec & then declines over
next 4msec.
Voltage rises above the RMP (becomes less –ve)
→Excitatory postsynaptic potentials (EPSP).

Excitatory because if this potential rises high enough in
the +ve direction it elicits action potential in the post
synaptic neuron.
Thus ↑ the excitability of that neuron to other stimuli.
EPSP of +20mv i.e from – 65mv to – 45mv initiates
action potential.
Ionic basis of EPSP :
1)Opening of chemical/ligand gated (Na or Ca) ion
channels in postsynaptic neuron.
2) ↓ conductance through Cl & K channels.
3) ↑ the number of excitatory membrane receptors or
4) ↓ number of inhibitory membrane receptor.

Fast excitatory post synaptic
potential (EPSP) transmission
Na+
Na+
Ca2+
Ca2+
• Opening of voltage gated Ca++ channels-Ca++ enters

Na+
Na+
Ca2+
Ca2+
• Fusion of docked vesicles with terminal memb. (Active zones)

Na+
Na+
Ca2+
Ca2+
Fast excitatory post synaptic potential
(EPSP) transmission
• Release of NT by exocytosis

Na+
Na+
Ca2+
Ca2+
Na+
Na+
-70mV
Excitatory
postsynaptic
potential (EPSP)
• NT bind with receptors on post synaptic memb - Opens Na+ channels (Na+ influx) –
positivity inside

Slow excitatory transmission
Na+
Na+
Ca2+
Ca2+
K+
K+

Slow excitatory transmission
Na+
Na+
Ca2+
Ca2+
-70mV
Slow EPSP
x
x
• Closure of K+ channels - no K+ efflux – positivity inside

Properties of postsynaptic potentials
• Mediated by ligand-gated channels
• Graded
• Decremental (ie local, non-propagated)
• Depolarising (excitatory) or hyperpolarizing
(inhibitory)
• Can summate
• Enable synaptic integration

If postsynaptic membrane receive impulses from
multiple nerve terminals, simultaneously at the same
time (spatial) or in rapid succession i.e. repeatedly
(Temporal) → the effect of all impulses (potentials) is
added up called as summation giving larger response.
If potential developed reaches threshold level →
developing an action potential at the initial segment
of the axon (axon hillock).
Cause : Large number of voltage gated Na channels
present at axon hillock as myelin sheath is absent
there. Also the threshold required here is less (6 to 10
mv).

Inhibitory postsynaptic potentials (IPSP) : Stimulation of
pre-synaptic terminals releases neuro transmitter 
hyperpolarization of the post-synaptic memb  IPSP.
It begins about 1 to 1.5msec after afferent impulse
enters spinal cord, reaches peak 1.5 -2 msec after its
onset & declines exponentially with time of about
3msec.
During this response there is ↓ in RMP i.e it becomes
more –ve. So threshold for excitation is ↑ (i.e the
excitability of the neuron to other stimuli is ↓ .
↑ in negativity of voltage beyond the RMP is called IPSP.
IPSP also summate spatially & temporally.

Ionic bases of IPSP:
1) Opening of Cl¯ channels of post-synaptic memb.
(produced by inhibitory neurotransmitter)  
excitability and membrane potential goes away
from firing level.
Also IPSP can be produced by:-
2) Opening of K+ channels  outward movement of K+
3)Closure of Na+ or Ca++ channels
4) Decrease in excitatory receptors
5) Increase in inhibitory receptors
5mV ↓ in RMP IPSP

Fast transmission of inhibitory
post synaptic potential (IPSP)
Na+
Na+
Ca2+
Ca2+

Na+
Na+
Ca2+
Ca2+
• Release of NT by exocytosis
Fast transmission of inhibitory post synaptic
potential (IPSP)

Na+
Na+
Ca2+
Ca2+
Cl-
Cl-
-70mV
Inhibitory
postsynaptic
potential (IPSP)
• NT bind with receptors on post synaptic memb –Opens
Cl- channels (Cl- influx)-Negativity inside
Fast transmission of inhibitory
post synaptic potential (IPSP)

Slow transmission of inhibitory post
synaptic potential (IPSP)
Na+
Na+
Ca2+
Ca2+

Na+
Na+
Ca2+
Ca2+
K+
K+
• NT bind with receptors on post synaptic memb –
Opens K+ channels (K+ efflux)
Slow transmission of inhibitory post
synaptic potential (IPSP)

Slow inhibitory post synaptic
potential-IPSP
Na+
Na+
Ca2+
Ca2+
-70mV
Slow IPSP
K+
K+
• Produces negativity inside postsynaptic memb.

EPSP
(Excitatory postsynaptic potential)
• Opening of Na channels
• K & Cl channels are not
opened.
Both the above actions
cause increased positivity
of the neuron and so
excitation that can lead
to depolarization & AP….
IPSP
(Inhibitory postsynaptic potential)
• Opening of Cl channels &
chloride ion influx
• Increased efflux of K ions
Both cause increased
negativity inside the
neuron leading to
hyperpolarization and
inhibition of the neuron.
Thus, AP will NOT be
initiated.

Fate of the Neurotransmitter:
Dissociates from the Receptor & can have either of
the 3 fates:
• Enzymatic Degradation: A portion of it is
inactivated by the enzymes present in high
concentration at the postsynaptic membrane.
• Re-uptake of remaining NT by Pre-synaptic neuron
and Re-used.
• Diffusion into the blood stream.
• Inactivation of neurotransmitter is essential
otherwise it will produce prolonged stimulation of
the post synaptic neuron in response to single
impulse in the presynaptic neuron.

Inactivation of Neurotransmitters
e.g. Ach
e.g. Serotonin
e.g. NE

Development of Action Potential
Development of AP from EPSP has three steps:
1) Synaptic integration
2) Generation of initial segment spike &
3) Generation of propagated signals i.e. action
potential.

Synaptic integration: Phenomena of summation
(temporal & spatial) of both EPSP & IPSP produced
at the postsynaptic membrane.
Net algebraically summated potential determines
whether synaptic transmission will occur or not.

Generation of initial segment spike :
The summated EPSP & IPSP spread passively to the
initial segment (Axon hillock & proximal part of initial
segment of unmyelinated nerve fibres).
If summated potential depolarizes axon hillock/initial
segment to threshold of 6 -10 mV (low threshold is
required), a spike potential – initial spike (IS) is
generated.
Magnitude is 30 – 40mV above the threshold level.

Generation of propagated signals i.e. action potential :
Initial segment spike initiated → itself produces further
depolarization of 30 -40 mV by opening of voltage gated
Na channels (abundant) on axon hillock.
Thus initial segment (IS) spike in turn triggers the
generation of action potential (AP) spike.
AP travels in both directions –
a) peripherally in the axon as nerve impulse

b) Retrogradely over postsynaptic cell membrane
& dendrites to clear the previous summated
potential.
Backward conduction called as soma dendritic
(SD) spike.
Thus after synaptic transmission, post synaptic
neuron (soma & dendrites) returns back to resting
potential. It allows fresh EPSP & IPSP to be
generated & fresh summation to occur.

PROPERTIES OF SYNAPSES:
1)Synaptic delay
2)Law of forward conduction
3)Convergence & divergence
4)Summation – a)Spatial & b)Temporal
5)Inhibition – a)Direct b)indirect c)Presynaptic inhibition
6)Facilitation
7)Occlusion
8)Subliminal fringe
9)Fatigue, Site of fatigue
10)Plasticity -a)Habituation & sensitization
b) Post tetanic potentiation
c) Long term potentiation &
d)Long term depression
11) reverberating circuit

1. Synaptic delay (Irreducible)
Definition: Synaptic delay: Time required for the
transmission of signal from Pre to Postsynaptic neuron.
i.e about 0.5msec.
Cause :1) Discharge of neurotransmitter from the
presynaptic membrane.
2) Diffusion of neurotransmitter across the synaptic
cleft to reach the post synaptic membrane.
3) Binding of neurotransmitter to the neuroreceptors.
4) Action of the receptor to ↑ the membrane
permeability.
5) Inward diffusion of Na to ↑ excitatory postsynaptic
potential to threshold to elicit the Action Potential.

Significance : Synaptic delay - rate-limiting step of
neural transmission.
In polysynaptic pathway conduction is slow.
From total synaptic delay we can know number of
synapses.
To calculate total synaptic delay the neuro physiologist
measure total duration taken by stimulus to travel &
show response. Suppose it is 1sec.
Type of nerve fibre - conduction velocity is known.
Let it be 20m/ sec.
Measure actual length of that peripheral nerve.
From muscle end to vertebral or spinal end. Suppose it
is 20cm.

As conduction velocity is 20metres/sec i.e
2000cm/1000msec.
i.e. 2000cm distance travelled in 1000msec.
20cm in X msec
X =10msec.
Synaptic delay = Total duration – duration for
nerve transmission through nerve.
i.e , 1sec (1000msec) – 10msec = 990 msec.
Therefore number of synapses = 990/0.5 = 198
Hence polysynaptic pathway, so conduction slow.
Synaptic delay extremely short in electrical
transmission as no neurotransmitter release.

2. Law of forward (one-way) conduction
Axon can transmit impulse in both direction.
But in synapse conduction in one direction i.e
orthodromically (wiping the slate clean) from
presynaptic to the postsynaptic neuron not antidromic.
Cause : 1)Chemical mediator at synaptic junction is
located in synaptic knob (presynaptic terminal) &
receptors only on postsynaptic membrane.
2) Also number of Na channels (voltage gated) is less
on soma & dendrites so no adequate depolarisation &
action potential.

In electrical synapses:
The transmission of impulses is bidirectional as
pre & postsynaptic membranes are in close
apposition, often fused at several points & have
cytoplasmic continuity.
Significance : Synapse due to one way direction
determines the direction of an impulse.
This is necessary for orderly neural function.

3) Convergence & divergence :
Convergence : Many presynaptic neurons converge i.e
meet at a common focus on any single postsynaptic
neuron. e.g. Anterior horn cells or motor neurons of
spinal cord.
Impulses come from long descending pathways, also
from dorsal root & interneurons.
Motor neurons form Final Common Pathway.
Thus synapse acts as relay station but also act as
integrator (grading & adjusting neural activity) e.g.
cerebral cortex.
Divergence: Presynaptic neuron divide into many
branches that diverge to end on many postsynaptic
neurons. e.g. Divergence of visual impulses from
retina to Occipital cortex.

3)Divergence & Convergence
Divergence Visual impulses
(Retina to Occipital cortex)
Convergence
Spinal Motor neuron

4) Summation :
Fusion of effects or progressive increase in excitatory
post synaptic potential, when many presynaptic
terminals are stimulated simultaneously or
repeatedly.
Integration/ Summation - needed :
EPSP due to activity in one synaptic knob is small (0.5
-1mv) so cannot induce an action potential.
But during excitation in the neuronal pool many
presynaptic terminals are stimulated at the same
time, which are spread over wide areas of the
postsynaptic neuron.
But their effects (EPSPs) can summate.

Cause : Change in potential at any single point
within soma will change the potential everywhere
inside the soma exactly equally ( due to high
electrical conductivity inside the neuronal cell body.
So during each discharge of impulse the EPSP
becomes +ve by a fraction of millivolt when reaches
Threshold (↓ in –ve by 15 -20 mv) action potential is
generated in postsynaptic membrane.
IPSPs and EPSPs can cancel each other out.

Temporal summation : If successive stimuli from
one synaptic knob reach the postsynaptic
membrane rapidly ( before the decay of previous
stimuli) or one after the other.
The postsynaptic potential (PSP) generated during
each discharge is added up to the next PSP & high
PSP level is achieved.
Due to repeated excitation or facilitation of a
postsynaptic neuron.

• Spatial summation : If subminimal stimuli
from two or more different presynaptic knob
widely spaced reach a Postsynaptic neuron
simultaneously, their postsynaptic potentials
are added & if reaches threshold of firing
action potential is generated.
Cause : Activity of one synaptic knob
facilitates the activity in another due to more
release of neurotransmitter.
This is very important in central neural
transmission.

If simultaneous summation of inhibitory & excitatory
postsynaptic potentials occur, they partially or
completely nullify each other. This results in decrease or
completely turn off the activity of post synaptic neuron

5) Facilitation of Neurons :
• When one excitatory signal enters post synaptic
neuron there is generation of EPSP of 0.5 -1mv.
• If another excitatory signal arrives to the same
postsynaptic neuron this neurone is excited easily &
neuron is said to be facilitated due to beneficial
effect of previous stimulus.
• Advantage :Neurons respond quickly & easily as the
synaptic resistance is decreased for further
stimulation.

6) Inhibition : An active process which either prevents
onset of activity in the neuron or stops the activity already
present.
It may be Postsynaptic or Presynaptic.
Types of inhibitions known to occur at synapses –
1)Postsynaptic inhibition 2)Presynaptic inhibition
3)Feedback inhibition 4)Feed forward inhibition
5)Reciprocal inhibition
1)Postsynaptic inhibition :
i)Direct postsynaptic inhibition : Development of
inhibitory postsynaptic potential (IPSP)-Release of
inhibitory neurotransmitters(Ach, dopamine, glycine,
GABA) – partial hyperpolarization.

Ionic bases of IPSP:
1) Opening of Cl¯ channels of post-synaptic memb.
(produced by inhibitory neurotransmitter)  
excitability and membrane potential goes away
from firing level.
Also IPSP can be produced by:-
2) Opening of K+ channels  outward movement of K+
3)Closure of Na+ or Ca++ channels
4) Decrease in excitatory receptors
5) Increase in inhibitory receptors
5mV ↓ in RMP IPSP
e.g. Muscle spindle stretch reflex

Post synaptic Inhibition - Direct
Muscle spindle stretch reflex

e.g. Muscle spindle of extensor muscles when stretched
→ Stimulation of afferent nerves → impulses passes to
spinal motor neurons supplying same muscle & cause
EPSP which summate to produce action potential in
postsynaptic spinal motor neurons →so the
protoagonist muscle contracts.
At the same time these impulses also pass along
interneurons (Golgi bottle neurons) which liberate an
inhibitory transmitter glycine at their synaptic
connections with motor neurons supplying the
antagonist muscle. In these motor neurons i.e
postsynaptic neuron an IPSP is produced which results
in simultaneously reflex relaxation of its antagonists
(flexor).

Golgi tendon organ reflex

• Golgi tendon reflex

ii) Postsynaptic inhibition ( indirect inhibition):
It occurs due to effects of previous post synaptic
discharge.
a)Postsynaptic cell can be refractory to excitation
because it has just fired i.e. existing EPSP has not been
cleared by the soma dendritic (SD) spike (retrograde /
antidromic conduction).
b)During hyperpolarization postsynaptic neuron is less
excitable.

c)Renshaw cell inhibition (Negative feedback
inhibition):
Neurons inhibit themselves in a negative feedback
fashion e.g. axons of spinal motor neurons give
collateral branches as they travel towards the
ventral root.
These collaterals make excitatory synaptic
connections with interneurons called Renshaw cell.
These Renshaw cells in turn send axons which
make inhibitory synaptic connections with spinal
motor neurons.
Significance : Renshaw cells check the discharge of
those motor neurons. Similar collaterals are seen
in cerebral cortex & limbic system.

Post synaptic Inhibition
Indirect – Renshaw cell

2) Presynaptic inhibition : Occurs in axo axonal type of
synapse. Inhibition occurs at presynaptic terminal before
the signal reaches the synapse.
Caused by discharge of inhibitory interneuron which
releases the neurotransmitter GABA → opening of anion
channels which diffuse into presynaptic terminal.
These – ve charges cancel much of the excitatory effect of
the presynaptic terminal when action potential arrives to
it.
So less excitation of post synaptic membrane, weak EPSP
is developed or synaptic transmission is completely
stopped in postsynaptic membrane.

e.g. Presynaptic inhibition occurs in sensory pathways.
That is adjacent terminal nerve fibres mutually inhibit
one another which minimizes the side way spread of
signal in sensory tract.
Mechanisms :
i)↑ Cl- conductance →hyperpolarization of presynaptic
neuron, ↓ size of action potential reaching the excitatory
ending →↓ ca influx →↓ release of neurotransmitter.
ii)Voltage gated K+ channels open →↓ ca influx
iii) Direct inhibition of transmitter release independent of
Ca ++influx. GABA mediate presynaptic inhibition via G
protein → ↑ K + conductance or direct blocking of Ca
channels in presynaptic neuron.
Baclofen a GABA agonist is effective in treatment of
spasticity of spinal cord.

3) Feedback inhibition (Renshaw cell inhibition):
Via Renshaw cell the motor neurons check their own
activity.

• 4)Feed forward inhibition : Seen in cerebellum.
Here neuron is connected through two pathways:
one excitatory & other inhibitory. Granule cell
excites the Purkinje cells which is soon inhibited by
basket cell, which in turn was excited by granule
cell.
• This type of arrangement limits the duration of
excitation produced by any given afferent volley i.e.
allows a brief & precisely timed excitation.

Reciprocal inhibition:
• Phenomenon in which an afferent signal activates
an excitatory neuron to a group of muscles and
simultaneously activates inhibitory signals to other,
usually antagonistic muscles.
• For example, during flexion of a joint the afferent
stimulus causes excitation of the neurons supplying
the flexor muscles of the joint and at the same time
a branch of afferent fibre excites an inhibitory inter-
neuron, which synapses with the motor neuron
supplying the extensor muscles of the joint.

7) Subliminal fringe:
• Subliminal means below threshold & Fringe means
border line.
• Response obtained by simultaneous stimulation of
two presynaptic neurons is greater than the sum total
of response obtained when each presynaptic neuron
is stimulated separately.
• Explanation : Here the stimulus from each
presynaptic neurons is subminimal/subliminal. This
stimulus will be adequate for some of the
postsynaptic neurons & they will show response.

• But few postsynaptic neurons are high resistance
so inadequately stimulated & will not show
response to this single subminimal stimulus.
• When both presynaptic neurons fire
simultaneously the two subminimal stimuli
becomes adequate for the postsynaptic neurons
with high resistance & they also show response &
the effect seen is more than expected.
• It is another example of spatial summation.

8) Subliminal Fringe
A=3 B=3
A+B=12
Not discharged but
Increased excitability

8) Occlusion (block):
• Opposite to subliminal fringe.
• When two presynaptic neurons are stimulated
simultaneously with adequate stimulus, total response
in the postsynaptic neurons is less than the sum total
of response obtained when the two presynaptic
neurons are stimulated separately.
• Explanation : A & B are two presynaptic neurons each
stimulates ten postsynaptic neurons by adequate
stimulus.

• As the stimulus is adequate all neurons are excited.
• But when both presynaptic neurons are stimulated
simultaneously (15 neurons excited) i.e. actually the
effect seen is less.
• Cause : Common neuronal response remains same it
does not increase e.g. Impulse from motor cortex to
periphery, basal ganglia, cerebellum.

Occlusion
• Common to both
neurons
A=9 B=9
A+B=12

9) Fatigue :
• Excitatory synapses are repetitively stimulated at
rapid rate, initially ↑ in discharges at postsynaptic
neuron then decrease & finally disappearance of
response. This phenomenon is called synaptic
fatigue or habituation.
• Site of fatigue in CNS is synapse.
• CNS neurons cannot sustain O2 lack so first site of
fatigue of the synaptic chain is located in the brain.
• Importance : When areas of nervous system
become over excited, fatigue ↓ the excitability
after some time e.g. excessive excitability of the
brain during seizures (epilepsy) is ↓ & it stops.
• Thus it is protective & temporary mechanism.

• Cause :
1)Exhaustion of stores of neurotransmitter as the rate
of synaptic transmission, rate of synthesis of
neurotransmitter fails to keep pace.
2)↓ in release of neurotransmitter as inactivation of Ca
channel which decreases intracellular Ca.
3) Accumulation of metabolites.
4)Progressive refractiveness of postsynaptic membrane
5)Tachyphylaxis – Adaptation of receptor
6)Probable reason – more Ca inside the postsynaptic
membrane so K efflux so hyperpolarisation.

9) Synaptic plasticity :
• Capability to mould or change. Synaptic
conduction is increased or decreased on the basis
of past experience.
• These changes are Presynaptic or postsynaptic in
location & play important role in learning
(conditioned reflexes) & memory.
• Forms of synaptic plasticity:
i)Post-tetanic potentiation,
ii) Long-term potentiation
iii) Synaptic fatigue or habituation
iv) Sensitization and
v) Long-term depression.

i) Post-tetanic potentiation:
• When a pre-synaptic neuron is stimulated with a
single stimulus, followed by stimulation with a
volley of (brief tetanizing stimuli) (says 100/s) for 2
stimulus and then again with a single stimulus, the
second stimulus evokes a larger post-synaptic
response than the first stimulus.
• This phenomenon is called post-tetanic
potentiation.
• This occurs due to that brief tetanizing stimuli in
the presynaptic neuron resulting in an increase in
intracellular Ca2+ due to increased Ca2+ influx.
• It is a form of synaptic facilitation.

ii) Long term potentiation :
• When post tetanic potentiation gets much more
prolonged & lasts for days , it is called as long term
potentiation.
• Cause : Increase in the intracellular Ca++ in the
post synaptic neuron rather than presynaptic
neuron.
• Commonly seen in hippocampus. LTP involves
protein synthesis, growth of pre & postsynaptic
neurons & their connections.

Presynaptic Facilitation
A P is prolonged & Ca++ channels remain open for long duration

(iii) Long-term depression (LTD):
• It is opposite to long-term potentiation. It is
characterized by a decrease in synaptic conduction
that occurs due to slow stimulation of presynaptic
neurons and associated with slow and decrease
Ca2+ influx.
• It was first noted in hippocampus and in
cerebellum.
• LTD of climbing fibres causing decreased firing of
parallel fibres.

(iv) Sensitization :
• Sensitization refers to a prolonged occurrence of
increased post-synaptic responses (response
intensified or potentiation of effect) after a
stimulus is paired once or several times with a
noxious stimulus.
• It is due to presynaptic facilitation of synaptic
transmission brought about by third neuron called
as facilitatory neuron which releases
neurotransmitter serotonin which further leads to
increase Ca influx & more release of
neurotransmitter at the presynaptic ending.

iv)Habituation:
• If benign Stimulus is presented for first time it
evokes response but if repeated produces lesser &
lesser response. Further no response to stimulation
• If stimulus is not harmful i.e. the subject
ignores/neglect it.
• Cause : Synapses decreases the intensity of
stimulus due to inactivation of Ca channels.

10) Reverberation :
• Phenomenon of passage of impulse from pre-
synaptic neuron and again back to pre-synaptic
neuron to cause a continuous stimulation of pre-
synaptic neuron.
• Nervous system is a network of fibres and in this
network, it is possible that a branch of axon of a
neuron may establish connection with its own
dendron.
• This causes reverberation of impulse through same
circuit again and again.
• This is prevented to some extent by phenomenon of
fatigue.

7. EFFECTS OF CHEMICAL CHANGES IN THE BLOOD:
• Acidosis depresses while alkalosis increases the
neuronal activity.
• Hypoxia exerts a depressing effect.

Synapse by sunita tiwale

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