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.

The Number of Components of Enhancement Contributing to Short-Term Synaptic Plasticity at the Neuromuscular Synapse during Patterned Nerve Stimulation Progressively Decreases As Basal Release Probability Is Increased from Low to Normal Levels by Changing Extracellular Ca2+

“…In contrast, at normal prob 0 , depression, typically indicated by a rundown of postsynaptic potential amplitudes during a train of impulses, can develop depending on the specific synapse and the stimulation rate (Liley and North, 1953;Mallart and Martin, 1968;Magleby, 1973b;Wu and Betz, 1998;Dittman et al, 2000;Wesseling and Lo, 2002;Stevens and Williams, 2007). The contributions of F1, F2, A, and P to STP during depression are less clear, as previous studies suggest that some of the components of enhancement may no longer contribute for normal prob 0 (Dittman et al, 2000;Kandaswamy et al, 2010;Müller et al, 2010).…”

“…The RRP is then replenished from a recycling pool (RP). The formulation used for depletion is similar to previous studies Stevens, 1997, 2001;Wu and Betz, 1998;Richards et al, 2003;Kalkstein and Magleby, 2004;Rizzoli and Betz, 2005;Neher and Sakaba, 2008;Pan and Zucker, 2009;Kandaswamy et al, 2010). Depletion occurs because vesicles are released from the RRP faster than they are replaced as follows:…”

“…The model is an extension of the quantal hypothesis proposed by del Castillo and Katz (1954) that often serves as a starting point for more extensive models of transmitter release (Varela et al, 1997;Wu and Borst, 1999;Dittman et al, 2000;Zucker and Regehr, 2002;Trommershäuser et al, 2003;Kalkstein and Magleby, 2004;Pan and Zucker, 2009;Kandaswamy et al, 2010) as follows:…”

“…Whereas application of natural stimulation patterns serves the same purpose while allowing the critical decoding of natural synaptic input (Dittman et al, 2000;Hermann et al, 2009;Kandaswamy et al, 2010), such irregular stimulation does not readily allow direct visual observation of the components and their time course, as is the case when step changes in stimulation rate are applied systematically.…”

“…A characteristic property of such synapses is that the amount of transmitter released from nerve terminals by each action potential can change dramatically during a train of impulses (Cowan et al, 2001;Atwood and Karunanithi, 2002;Zucker and Regehr, 2002;Neher and Sakaba, 2008). These changes, referred to as short-term synaptic plasticity (STP), have dramatic reversible effects on synaptic strength (Liley and North, 1953;Zengel et al, 1980;Magleby and Zengel, 1982;Dittman et al, 2000;Wesseling and Lo, 2002;Abbott and Regehr, 2004;Pan and Zucker, 2009;Kandaswamy et al, 2010;Müller et al, 2010).…”