Stochastic, structural and functional factors influencing AMPA and NMDA synaptic response variability: a review

Abstract

Synaptic transmission is the basic mechanism of information transfer between neurons not only in the brain, but along all the nervous system. In this review we will briefly summarize some of the main parameters that produce stochastic variability in the synaptic response. This variability produces different effects on important brain phenomena, like learning and memory, and, alterations of its basic factors can cause brain malfunctioning.

Information Processing and Synaptic Transmission

“…The big problem in this respect is to identify if this type of system depends really on stochastic processes or if stochasticity is apparent because the lack of the full information needed to characterize the processes. From the most top point of view, almost all the causes of EPSP variability described herein can appear of stochastic type [8,[32][33][34]], but we cannot definitively exclude that the apparent stochasticity is due to our incomplete understanding of all the underlying mechanisms and/or to the lack of knowledge of all the steps underlying the process. Just to give an example, if we consider the response variability depending on the number of molecules in the vesicle, its position on the AZ (eccentricity), and its variable release probability, [8,17,[27][28][29][32][33][34] we can assume a stochastic origin of the presynaptic factors of the synaptic response variability.…”

“…This is especially true for the causes of variability of the EPSP. EPSP variability can be due (a) to stochastic processes [8,[32][33][34] or (b) to specific systems of regulation which operate at different levels of the synaptic transmission (intrasynaptic or extrasynaptic). About the stochastic variability, we cannot say too much.…”

“…Essentially, the different modulation systems produce a sort of complex nonlinear variability of the postsynaptic response. Variability of the EPSP is caused both by pre-and postsynaptic mechanisms of control, and a part of this variability seems to be of stochastic nature (for a review see [8]). In the following we will examine some (but not all) regulatory mechanisms which imply modulation of variability of the postsynaptic response and their possible stochastic and/or deterministic nature.…”

“…A variable number of molecules produce EPSC with different amplitude [32][33][34][36][37][38]. In our early work on single glutamatergic response, we have considered the combination of the number of molecules and the position of release as stochastic factors [8,[32][33][34]. However, by considering the large variability of the concentration of glutamate in the vesicles, the thousand possible combinations of "position-number of molecules," this could be a powerful system of presynaptic regulation of the information transfer.…”

“…In this framework, a great amount of complexity depends on the mechanisms which regulate the transmission of a single bit (spike) information to each synapse. The synaptic activity is greatly influenced by many factors [8]. First of all, the way glutamatergic synapse contributes to the postsynaptic neuronal code depends strongly on the biophysical properties of the dendrite where the synapse is located and on the path from its location to the soma.…”