1. Synaptic transmission
Mostly focus on presynaptic models
Some postsynaptic receptors: have been shown in class
John Jacques

2. Communication between neurons
Background
Communication between neurons

3. Communication between neurons
Background
Communication between neurons
Staggering diversity of synapse morphologies and types in the brain
Fundamental process of synaptic transmission same
A key quantity in neural circuits is the synaptic efficacy or strength, which varies over time.
long-term potentiation and depression
constitute the basis of learning and memory

4. Synaptic Transmission Principles
Arrival of an action potential
Release of neurotransmitter
Binds to receptors
Generate a response in the postsynaptic neuron

5. Synaptic vesicle cycle
Docked vesicles lie close to plasma membrane (within 30 nm)
Primed vesicles
fuse with the plasma membrane by sustained depolarization
high K+, elevated Ca++, hypertonic sucrose treatment
Fusion
release transmitter
near calcium channels
The ‘active zone’
Exocytosis
Endocytosis
Reserve pool (80-95%)
Recycling pool (5-20%)
Readily-releasable pool (0.1-2%; 5-10 synapses per active zone)

6. EPSP and IPSP Excitatory Neurotransmitters: ACh and glutamate
Inhibitory Neurotransmitters:
Glycine and GABA

7. Postsynaptic effects

8. Transmitter release
T(t): amount of transmitter released into the synaptic cleft at time t.
N(t) available for release vesicles
changes over time since the occupancy of the pool changes during neural activity
p(t)release probability
dramatically increases upon the arrival of a presynaptic AP
Focus on the action of ionotropic receptors
ion channel that opens when transmitter is bound

9. Postsynaptic conductance
proportional to the amount of transmitter released
Equation 2 above
peak conductance is denoted by gm

10. Outline Short term plasticity Vesicle depletion and facilitation
discuss biological background and plausibility
Mechanistic aspects of these models
Vesicle depletion and facilitation
Use-dependent vesicle replenishment
Receptor desensitization
Stochasticity of synapses
Outlook/Conclusion

11. Short term plasticity Synaptic depression and facilitation
Depression: progressive reduction of the postsynaptic response during repetitive presynaptic activity
Facilitation: an increase synaptic efficacy.
Different mechanisms with different time constants
Not mutually exclusive
most synapses express some combination of these two mechanisms
Variable between different neuron types

12. Short term plasticity: PSD
STP: Factors located in the presynaptic terminal
contain vesicles filled with neurotransmitter
Opposed by the postsynaptic density (PSD)
Area that contains a large number of different proteins implicated in synapse maintenance and plasticity
contains the bulk of the neurotransmitter receptors mediating the postsynaptic response

13. Short term plasticity: PSD
Opening of voltage gated calcium channels (VGCC)
Intracellular concentration increase
increases the probability of vesicle fusion with the cell membrane
subsequent release of transmitter into the synaptic cleft (equation 1)
activity-dependent; function of time.
[Ca2+]i and release probability p not linear
The release of a single vesicle
smallest signal transmitted to the postsynaptic neuron
spontaneous current
small fraction in terminal in AZ

14. Vesicle depletion model : depletion
Presynaptic vesicles are a limited resource
during ongoing activity
can lead to a suppression of the postsynaptic response
model predicts an exponential decay of the postsynaptic response (A)
Time constant order of seconds
Faster decay- higher p
steady state values decrease more slowly with increasing frequency (E)
Suggests other mechanism

15. Vesicle depletion model : facilitation
Depression model counteracted by facilitation
accumulation of residual calcium in the synaptic terminal
causes rapid VGCC facilitation
increases the release probability after each presynaptic spike
Time constant : range of tens of milliseconds
much faster than vesicle replenishment

16. Use-dependent vesicle replenishment
accelerate after intensive stimulation.
increase in intracellular calcium concentration
Enhanced vesicle replenishment
included in the depletion model
adding some form of activity-dependent component to Equation (7)
Use-dependent replenishment
reflect faster recruitment due to more efficient endocytosis
A main function of mechanism
maintain the ability of a synapse to transmit during sustained periods of high activity

17. RECEPTOR DESENSITIZATION
THE OTHER SIDE:
RECEPTOR DESENSITIZATION
Synaptic depression due to desensitization
the state of the population of receptors D(t) (10)
Recovery from desensitization
order of tens of milliseconds
only effective during intense episodes of activity
desensitization
important property of receptors
contribute to synaptic depression during physiological activity levels

18. Stochasticity of synapses
Transmitter release
postsynaptic current fluctuates from time to time.
Changes in the synaptic parameters due to short term plasticity
cause changes in the average postsynaptic response
magnitude of the fluctuations
measured by the coefficient of variation: (11)

19. Outlook/Conclusion
Theoretical models have contributed much to our understanding of synaptic transmission and short term plasticity
Relationship between depletion and facilitation
key variables in these models have direct measurable correlates
Not straight forward to experimentally interfere with short term plasticity  
Valuable tool that enables analysis beyond the experimentally feasible.
Short term plasticity may related to homeostatic effects or metabolic efficacy of synapses

20. Hennig, Matthias H. “Theoretical Models of Synaptic Short Term Plasticity.” Frontiers in Computational Neuroscience 7 (2013): 45. PMC. Web. 3 Oct
Destexhe, A., Mainen, Z. and Sejnowski, T. (1994). Synthesis of models for excitable membranes, synaptic transmission and neuromodulation using a common kinetic formalism. Journal of Computational Neuroscience, [online] 1(3), pp Available at: [Accessed 2 Oct. 2017].
REFENCES

21. QUESTIONS??