Synaptic transmission between neurons occurs either electrically or chemically. In electrical transmission, gap junctions allow ions to pass directly between neurons. In chemical transmission, neurotransmitters are released from vesicles in the presynaptic neuron and bind to receptors in the postsynaptic neuron. The process involves neurotransmitter synthesis, storage in vesicles, calcium-triggered release, binding to receptors, and termination of signaling via reuptake or enzymatic degradation. Chemical transmission is slower but allows for signal modulation, in contrast to electrical transmission.

3. Synaptic transmission
• Impulses are transmitted from one nerve cell to another cell at the
synapses via the process of synaptic transmission or neurotransmission.
• Types of neurotransmission
1. electrical
2. chemical

4. Process of electrical transmission
• In the electrical synapse, the membranes of presynaptic and
postsynaptic cell come close together and gap junctions are formed
between them.
• These junctions form low resistance bridges through which the ions can
pass with relative ease.

5. Process of Chemical Neurotransmission
• In the process of chemical neurotransmission, neurotransmitters are
released from presynaptic neuron and it bind to the receptors located
on postsynaptic neuron.
Steps :
1. Synthesis and storage of neurotransmitter
2. Release of neurotransmitter
3. Binding of neurotransmitter to the postsynaptic receptors
4 Termination of action of released transmitter

7. Electrical Vs Chemical Neurotransmission
Electrical neurotransmission Chemical neurotransmission
Transmission by gap junctions Transmission by neurotransmitters
Bidirectional neurotransmission Unidirectional neurotransmission
Rapid impulse transmission Slow impulse transmission
Synaptic plasticity is absent Synaptic plasticity is present
Signal modification or magnification is not
possible
Signal modification or magnification is
present

8. Synthesis of neurotransmitters &
neuropeptides
• Neurotransmitters (Ach, GABA, glutamate) are synthesized in the nerve
endings.
• Neuropeptides (substance P, enkephalin, vasopressin) are synthesized
in nerve cell body.

9. Storage of neurotransmitters & neuropeptides
• Neurotransmitters are stored in small clear core and small dense core
vesicles.
• Neuropeptides are stored in large dense core vesicles.
• Vesicles and the proteins contained in their walls are synthesized in
neuronal cell body and then transported to the axon terminal by fast
axonal transport.
• Small vesicles are recycled in the nerve ending.

10. Synaptic vesicle proteins
Synaptic vesicle protein Function
1. Proton transporter / ATPase Influx of H+ (acidifies the
lumen)
2. Vesicular associated
transporter (VAT)
Antiporter- influx of
neurotransmitter and efflux of
H+
3. Synapsin Tethers the vesicle to actin
cytoskeleton
4. Synaptobrevin Component of SNARE complex
(v-snare)- facilitates vesicle fusion
5. synaptotagmin Calcium sensor, facilitates fusion
6. Rab3 GTP binding protein, role in
vesicle targeting

11. Release of neurotransmitters

12. Release of neurotransmitters
• Synaptic vesicles at the presynaptic terminal could be present near the active
zone or in the active zone.
• First influx of Ca2+ will cause the translocation of vesicles located outside the
active zone to the active zone and vesicles inside the active zone will be
released to move to the release site.
• The later will undergo docking and priming and keep themselves in fusion
ready state.
• On the second influx of Ca2+, the fusion ready state vesicles will complete its
fusion and thus release of neurotransmitter.
• On the other hand, the translocated vesicles in the active zone will undergo
priming and docking and now they are in fusion ready state.
• Also new vesicles will now be moved to the active zone and this cycle will
continue.

13. Steps of release of neurotransmitters
1. Arrival of action potential at axon terminal.
2. Opening of voltage gated Ca2+ channels.
3. Ca2+ influx and increase in intracellular calcium concentration.
4. Intracellular Ca2+ activate calmodulin which will then activate
calmodulin dependent protein kinase II. It will phosphorylate the
synapsin protein and thus release the vesicles from actin cage.
5. The vesicles then fall into the active zone of presynaptic terminal.
6. After translocation of vesicles to the active zone, docking will happen.
Docking is the process of recruiting the vesicles at the release site.

14. 7. It will be followed by priming which makes the vesicle release
competent such that it can fuse with the plasma membrane when the
trigger (calcium) arrives. It involves partial SNARE complex formation
(SNARE complex with complexin (inhibits fusion) )
8. After docking and priming of synaptic vesicles, the vesicles are now in
fusion ready state
9. On second influx of Ca2+, synaptogamin will sense it and thus bind to
assembled SNARE complex and displace the complexin. Hence
complete the SNARE complex formation.

15. SNARE Complex formation
• SNARE stands for soluble NSF attachment protein receptor (SNAP receptor)
• It is a large family of proteins which mediates vesicle fusion.
• SNARE proteins which mediates neurotransmitter release of synaptic vesicles in neuron are
synaptobrevin (VAMP), syntaxin and synaptosomal associated protein of 25 kDa (SNAP
25).
• Vesicle-associated proteins, such as VAMP, are referred to as v-SNAREs, and those of the
target membrane, such as SNAP-25 and syntaxin, are referred to as t-SNAREs
• SNAREs bind to each other to form a very stable four-stranded coiled-coil core complex
called SNARE complex. Neuronal core complexes are formed by one coil each from
syntaxin and VAMP, and two coils from SNAP-25.
• This will lead to fusion pore formation and release of neurotransmitter.

17. • Two types of fusion
1. Incomplete fusion (Kiss and run discharge)
2. Complete fusion
• Incomplete fusion (kiss and run discharge)- Main vesicle stays inside the
cell and content will be discharged through a small pore and then the
opening is resealed rapidly.
• Complete fusion – involves the flattening of the vesicle onto the
membrane surface and taken up inside the cell by clathrin- mediated
endocytosis.

18. Duration of release of neurotransmitter
• The entire process, from the opening of Ca2+ channel to
neurotransmitter release, may occur quickly within 200 microseconds
or take up to 50 milli-seconds.
• It depends upon the location of pre-synaptic vesicles when Ca2+ enters
the neuron.
• For rapid release it is assumed that the some of the vesicles are in
fusion-ready state i.e. they are already docked and primed and thus all
the time will be consumed by the fusion step only.
• In delayed reactions, synaptic vesicles must be recruited and guided to
the active zones before neurotransmitter release can occur.

19. Need of vesicle recycling
• Active neurons are in constant need of transmitter filled vesicle which is
ready to release their contents.
• E.g. A terminal bouton in CNS neuron = 200 vesicles
• One AP will release = 1 to 2 vesicles
• Rate of impulse generation by neuron = 5 hertz
• Vesicle release in 1 minute = 5 × 60 = 300 minutes
i.e. in less a minute, all the vesicles will be consumed.

20. Recycling of synaptic vesicle (Exo-endocytic
cycle)

21. Recycling of vesicle
Recycling by clathrin mediated
endocytosis
Removal of the clathrin coat
Fusion of endocytosed vesicle
with early endosome
New vesicle formed from
budding off endosome
Direct reclosing of fusion pore
and reformation of vesicle
Reloading of vesicle with
neurotransmitter
Vesicle is ready for release
Complete fusion Kiss and run
discharge

22. Binding of neurotransmitter to the
postsynaptic receptors
• Neurotransmitter will bind to receptors located on postsynaptic neuron
to generate either excitatory (EPSP) or inhibitory synaptic potentials
(IPSP).

23. Termination of action of released
neurotransmitter
• Released neurotransmitter has to be cleared from the synaptic cleft to
terminate the action of it otherwise the receptor will be in continuous
state of excitation which can be harmful.
• It can be done by three ways:
1. Enzymatic degradation of neurotransmitter
2. Reuptake of neurotransmitter by the presynaptic neuron
3. Diffusion of neurotransmitter to the surroundings of synaptic cleft.

24. Upcoming video
• How neurotoxins act ?
• Properties of Synapse
• Action Potential