The Role of Presynaptic Dynamics in Processing of Natural Spike Trains in Hippocampal Synapses

Abstract

Short-term plasticity (STP) represents a key neuronal mechanism of information processing. In excitatory hippocampal synapses, STP serves as a high-pass filter optimized for the transmission of information-carrying place-field discharges. This STP filter enables synapses to perform a highly nonlinear, switch-like operation permitting the passage and amplification of signals with place-field-like characteristics. Because of the complexity of interactions among STP processes, the synaptic mechanisms underlying this filtering paradigm remain poorly understood. Here, we describe a simple mechanistic model of STP, derived in large part from basic principles of synaptic function, that reproduces this highly nonlinear synaptic behavior. The model, formulated in terms of release probability, considers the interactions between calcium-dependent forms of presynaptic enhancement and their impact on vesicle pool dynamics, which is described using a two-pool model of vesicle recruitment. By considering the interdependency between release probability and various forms of STP, the model attempts to provide a realistic coupling among major presynaptic processes. The model parameters are first determined using synaptic dynamics during constant-frequency stimulation. The model then accurately reproduces all major characteristics of the synaptic filtering paradigm during natural stimulus patterns without free parameters. An elimination approach is then used to identify the contribution of each STP component to synaptic dynamics. Based on this analysis, the model predicts strong calcium dependence of synaptic filtering properties, which is verified experimentally in rat hippocampal slices. This simple model may thus offer a useful framework to further investigate the role of STP in neural computations.