Transmission of temporally correlated spike trains through synapses with short-term depression

Short-term synaptic depression, caused by depletion of releasable neurotransmitter, modulates the strength of neuronal connections in a history-dependent manner. Quantifying the statistics of synaptic transmission requires stochastic models that link probabilistic neurotransmitter release with presynaptic spike-train statistics. Common approaches are to model the presynaptic spike train as either regular or a memory-less Poisson process: few analytical results are available that describe depressing synapses when the afferent spike train has more complex, temporally correlated statistics such as bursts. Here we present a series of analytical results—from vesicle release-site occupancy statistics, via neurotransmitter release, to the post-synaptic voltage mean and variance—for depressing synapses driven by correlated presynaptic spike trains. The class of presynaptic drive considered is that fully characterised by the inter-spike-interval distribution and encompasses a broad range of models used for neuronal circuit and network analyses, such as integrate-and-fire models with a complete post-spike reset and receiving sufficiently short-time correlated drive. We further demonstrate that the derived post-synaptic voltage mean and variance allow for a simple and accurate approximation of the firing rate of the post-synaptic neuron, using the exponential integrate-and-fire model as an example. These results extend the level of biological detail included in models of synaptic transmission and will allow for the incorporation of more complex and physiologically relevant firing patterns into future studies of neuronal networks.Author summary: Synapses between neurons transmit signals with strengths that vary with the history of their activity, over scales from milliseconds to decades. Short-term changes in synaptic strength modulate and sculpt ongoing neuronal activity, whereas long-term changes underpin memory formation. Here we focus on changes of strength over timescales of less than a second caused by transitory depletion of the neurotransmitters that carry signals across the synapse. Neurotransmitters are stored in small vesicles that release their contents, with a certain probability, when the presynaptic neuron is active. Once a vesicle has been used it is replenished after a variable delay. There is therefore a complex interaction between the pattern of incoming signals to the synapse and the probablistic release and restock of packaged neurotransmitter. Here we extend existing models to examine how correlated synaptic activity is transmitted through synapses and affects the voltage fluctuations and firing rate of the target neuron. Our results provide a framework that will allow for the inclusion of biophysically realistic synaptic behaviour in studies of neuronal circuits.