AbstractShort-term synaptic plasticity (STP) critically affects the processing of information in neuronal circuits by reversibly changing the effective strength of connections between neurons on time scales from milliseconds to a few seconds. STP is traditionally studied using intracellular recordings of postsynaptic potentials or currents evoked by presynaptic spikes. However, STP also affects the statistics of postsynaptic spikes. Here we present two model-based approaches for estimating synaptic weights and short-term plasticity from pre- and postsynaptic spike observations alone. We extend a generalized linear model (GLM) that predicts postsynaptic spiking as a function of the observed pre- and postsynaptic spikes and allow the connection strength (coupling term in the GLM) to vary as a function of time based on the history of presynaptic spikes. Our first model assumes that STP follows a Tsodyks-Markram description of vesicle depletion and recovery. In a second model, we introduce a functional description of STP where we estimate the coupling term as a biophysically unrestrained function of the presynaptic inter-spike intervals. To validate the models, we test the accuracy of STP estimation using the spiking of pre- and postsynaptic neurons with known synaptic dynamics. We first test our models using the responses of layer 2/3 pyramidal neurons to simulated presynaptic input with different types of STP, and then use simulated spike trains to examine the effects of spike-frequency adaptation, stochastic vesicle release, spike sorting errors, and common input. We find that, using only spike observations, both model-based methods can accurately reconstruct the time-varying synaptic weights of presynaptic inputs for different types of STP. Our models also capture the differences in postsynaptic spike responses to presynaptic spikes following short vs long inter-spike intervals, similar to results reported for thalamocortical connections. These models may thus be useful tools for characterizing short-term plasticity from multi-electrode spike recordings in vivo.Author SummaryInformation processing in the nervous system critically depends on dynamic changes in the strength of connections between neurons. Short-term synaptic plasticity (STP), changes that occur on timescales from milliseconds to a few seconds, is thought to play a role in tasks such as speech recognition, motion detection, and working memory. Although intracellular recordings in slices of neural tissue have identified synaptic mechanisms of STP and have demonstrated its potential role in information processing, studying STP in intact animals, especially during behavior, is experimentally difficult. Unlike intracellular recordings, extracellular spiking of hundreds of neurons simultaneously can be recorded even in behaving animals. Here we developed two models that allow estimation of STP from extracellular spike recordings. We validate these models using results from in vitro experiments which simulate a realistic synaptic input from a population of presynaptic neurons with defined STP rules. Our results show that both new models can accurately recover the synaptic dynamics underlying spiking. These new methods will allow us to study STP using extracellular recordings, and therefore on a much larger scale than previously possible in behaving animals.
Synaptic plasticity, neural circuits, and the emerging role of altered short-term information processing in schizophrenia
