Insights on synaptic paired-pulse response using parametric and non-parametric models.

Paired-pulse protocol is a well-established stimulation pattern used to characterize short-term changes in synaptic potency. Due to the experimental difficulty in accessing and measuring responses and interactions between subsynaptic elements, understanding the mechanisms that shape synaptic response is extremely challenging. We already proposed to address this issue and gain insights on the matter using a complex integrated modeling platform called EONS (Elementary Objects of the Nervous System). The use of this parametric platform provided us with insightful information on the subsynaptic components and how their interactions shape synaptic dynamics. We herein propose to add and combine a non-parametric model to (i) simplify the modeling framework, the number of underlying parameters and the overall computational complexity while faithfully maintaining the desirable synaptic behavior and (ii) provide a clear and concise framework to characterize AMPA and NMDA contributions to the observed paired-pulse responses.