PT - JOURNAL ARTICLE AU - Abed Ghanbari AU - Naixin Ren AU - Christian Keine AU - Carl Stoelzel AU - Bernhard Englitz AU - Harvey A. Swadlow AU - Ian H. Stevenson TI - Modeling the short-term dynamics of <em>in vivo</em> excitatory spike transmission AID - 10.1101/475178 DP - 2020 Jan 01 TA - bioRxiv PG - 475178 4099 - http://biorxiv.org/content/early/2020/04/04/475178.short 4100 - http://biorxiv.org/content/early/2020/04/04/475178.full AB - Information transmission in neural networks is influenced by both short-term synaptic plasticity (STP) as well as non-synaptic factors, such as after-hyperpolarization currents and changes in excitability. Although these effects have been widely characterized in vitro using intracellular recordings, how they interact in vivo is unclear. Here we develop a statistical model of the short-term dynamics of spike transmission that aims to disentangle the contributions of synaptic and non-synaptic effects based only on observed pre- and postsynaptic spiking. The model includes a dynamic functional connection with short-term plasticity as well as effects due to the recent history of postsynaptic spiking and slow changes in postsynaptic excitability. Using paired spike recordings, we find that the model accurately describes the short-term dynamics of in vivo spike transmission at a diverse set of identified and putative excitatory synapses, including a thalamothalamic connection in mouse, a thalamocortical connection in a female rabbit, and an auditory brainstem synapse in a female gerbil. We illustrate the utility of this modeling approach by showing how the spike transmission patterns captured by the model may be sufficient to account for stimulus-dependent differences in spike transmission in the auditory brainstem (endbulb of Held). Finally, we apply this model to large-scale multi-electrode recordings to illustrate how such an approach has the potential to reveal cell-type specific differences in spike transmission in vivo. Although short-term synaptic plasticity parameters estimated from ongoing pre- and postsynaptic spiking are highly uncertain, our results are partially consistent with previous intracellular observations in these synapses.Significance Statement Although synaptic dynamics have been extensively studied and modeled using intracellular recordings of post-synaptic currents and potentials, inferring synaptic effects from extracellular spiking is challenging. Whether or not a synaptic current contributes to postsynaptic spiking depends not only on the amplitude of the current, but also on many other factors, including the activity of other, typically unobserved, synapses, the overall excitability of the postsynaptic neuron, and how recently the postsynaptic neuron has spiked. Here we developed a model that, using only observations of pre- and postsynaptic spiking, aims to describe the dynamics of in vivo spike transmission by modeling both short-term synaptic plasticity and non-synaptic effects. This approach may provide a novel description of fast, structured changes in spike transmission.