Modeling Depressing Synapses

1. Modeling Depressing Synapses Ronen Elefant Sara Steenrod Parker Meeks ELEN E4011 Circuits in the Human Brain

2. Based on the paper Coding of Temporal Information by Activity-Dependent Synapses Written By: Galit Fuhrmann, Idan Segev, Henry Markram, and Misha Tsodyks ELEN E4011 Circuits in the Human Brain

3. Synaptic Transmission Extracellular fluid Synaptic cleft Nerve impulse • The occurrence of a stimulus causes a nerve impulse to travel down the pre-synaptic axon. The change in voltage triggers the opening of ion channels resulting in an influx of Calcium. Pre-synaptic cell Vesicles Receptors Axon Post-synaptic cell Figure from Carlos G. Finlay and Michael R. Markham at http://intro.bio.umb.edu ELEN E4011 Circuits in the Human Brain

4. Synaptic Transmission • The presence of Calcium enables the contents of pre-synaptic, neurotransmitter-filled vesicles to be released into the synaptic cleft. Figure from Carlos G. Finlay and Michael R. Markham at http://intro.bio.umb.edu ELEN E4011 Circuits in the Human Brain

5. Synaptic Transmission • The neurotransmitter molecules travel across the cleft to bind to appropriate receptors on the post-synaptic membrane. Binding of the post-synaptic receptors leads to the opening of ion channels. The influx and efflux of ions results in a change in membrane potential, or post-synaptic response (PSR). Figure from Carlos G. Finlay and Michael R. Markham at http://intro.bio.umb.edu ELEN E4011 Circuits in the Human Brain

6. Information Transfer • Information representing the stimulus is conveyed from the pre-synaptic cell to the post synaptic cell through the release of neurotransmitter and the resulting post-synaptic change in voltage. • How is this information represented? Potentially a combination of two mechanisms: • Rate code • Temporal Code ELEN E4011 Circuits in the Human Brain

7. Rate coding • Information is conveyed by the average firing rate of pre-synaptic input. • Problem: It is possible for completely different distributions of spikes to result in the same mean firing rate. ELEN E4011 Circuits in the Human Brain

8. Temporal coding • Information is conveyed by the timing of the pre-synaptic input. • Post-Synaptic Response could be influenced by the interspike interval (ISI). • Problem: How is the timing, or temporal coherence of the pre-synaptic input coded? ELEN E4011 Circuits in the Human Brain

9. Authors’ Goal • To create a biologically viable model to account for the dynamic changes in post-synaptic response (PSR) resulting from the timing of pre-synaptic inputs. • This model must incorporate the following constraints of synaptic transmission: • The amount of neurotransmitter used each time the pre-synaptic cell is stimulated. • The rate and probability with which the pre-synaptic cell recovers (i.e. the time it takes to replace and package neurotransmitter in vesicles and for vesicles to dock to the membrane to be ready for release). • The influence of these processes on the amount of neurotransmitter that actually binds to post-synaptic receptor resulting in a PSR. ELEN E4011 Circuits in the Human Brain

10. Resource Recovery This equation describes the interspike rate of resource recovery. ELEN E4011 Circuits in the Human Brain

11. Spike Amplitude Depends on Resources The amplitude of the spike is dictated by the amount of resources available. After a spike has occurred, the resources follow the same recovery equation, increasing the pool available for the next spike. ELEN E4011 Circuits in the Human Brain

12. Different values of USE for the Deterministic Model : USE = .2 : USE = .5 : USE = .8 USE is analogous to the probability of release in the quantal model of synaptic transmission. (Fuhrmann, 141) ELEN E4011 Circuits in the Human Brain

13. Post-Synaptic Response PSR is proportional to R (available resources) ELEN E4011 Circuits in the Human Brain

14. Deterministic Code ELEN E4011 Circuits in the Human Brain

15. Deterministic Code ELEN E4011 Circuits in the Human Brain

16. Probabilistic Model • A probabilistic model is useful to account for trial-to-trial fluctuations in observed synaptic responses. • Each release site may have at most one vesicle available for release. • Each vesicle is released with probability USE. Pv is analogous to the fraction of resources available for release. The probability of release depends on the product of the likelihood of the vesicle being available and the probability of it actually being released. ELEN E4011 Circuits in the Human Brain

17. Probabilistic Code ELEN E4011 Circuits in the Human Brain

18. Probabilistic Code ELEN E4011 Circuits in the Human Brain

19. Probabilistic vs. Deterministic Model Here the number of vesicles has a maximum value of 100. Note the deviation of the probabilistic values from the deterministic ones. = Probabilistic = Deterministic ELEN E4011 Circuits in the Human Brain

20. = Probabilistic = Deterministic = Number of Vesicles ELEN E4011 Circuits in the Human Brain

21. Biological application of depressing synapse model “Reading Neuronal Synchrony with Depressing Synapses” by: W.Senn, I Segev, M. Tsodyks • The authors examined activity from primary auditory cortex of the monkey when a stimulus (a tone) was presented: • The mean firing rate during stimulus presentation was, on average, the same for all stimuli. • However, the correlation of spike times were significantly higher during the stimulus presentation, which may indicate synchronous firing. ELEN E4011 Circuits in the Human Brain

22. How could synchrony solve “the binding problem”? • Binding problem: How are separate inputs associated with the features of an object combined to make a coherent whole? • Synchrony may be the answer—temporal correlation of firing patterns may provide the crucial information for assembling a complete representation of a stimulus from various inputs. • How does the depressing synapse do this? ELEN E4011 Circuits in the Human Brain

23. How does a depressing synapse enable synchronous firing? The authors modeled the pre-synaptic input with depressing synapses and non-depressing synapses: • With non-depressing synapses, the rate of pre-synaptic input is ineffective in raising the PSR above threshold during the stimulus. ELEN E4011 Circuits in the Human Brain

24. How does a depressing synapse enable synchronous firing? The authors modeled the pre-synaptic input with depressing synapses and non-depressing synapses: • With depressing synapses, the same pre-synaptic input is sufficient to cause the post-synaptic cell to respond during the stimulus presentation. ELEN E4011 Circuits in the Human Brain

25. How does synchronous firing affect the PSR? • When stimulated, a cell with a depressing synapse will exhibit a large initial burst of spikes which attenuates as resources are depleted. The cell recovers at a certain rate in order to fire again. • When a group of cells burst and recover in unison, the temporal summation of this input is sufficient to raise the PSR above threshold and yield a response. • The depressing synapse provides temporal organization for the input coming in to post-synaptic cell, enabling sufficient temporal summation to result in a unique PSR. • This mechanism reveals information, through a temporal code, about the stimulus which is not available with a non-depressing synapse. ELEN E4011 Circuits in the Human Brain

26. References • Allen C and Stevens CF. An evaluation of causes for unreliability of synaptic transmission. Proc Natl Acad SciUSA 91: 10380-10383, 1994. • Fuhrmann G, Segev G, Markham H, and Tsodyks M . Coding of Temporal Information by Activity-Dependent Synapses. J Neurophysiol 87: 140-147, 2002. • Senn W, Segev I, and Tsodysks, M . Reading Neuronal Synchrony with Depressing Synapses. Neural Computation 10: 815-819, 1998. • Tsodyks M and Markram H. The neural code between neocortical pyramidal neurons depends on neurotransmitter release probability. Proc Natl Acad Sci USA 94: 719-723, 1997. ELEN E4011 Circuits in the Human Brain

27. THE END ELEN E4011 Circuits in the Human Brain