250 words) 14 Information transmission in neural networks is influenced by both short-term synaptic plasticity 15(STP) as well as non-synaptic factors, such as after-hyperpolarization currents and changes in 16 excitability. Although these effects have been widely characterized in vitro using intracellular 17 recordings, how they interact in vivo is unclear. Here we develop a statistical model of the short-18 term dynamics of spike transmission that aims to disentangle the contributions of synaptic and 19 non-synaptic effects based only on observed pre-and postsynaptic spiking. The model includes a 20 dynamic functional connection with short-term plasticity as well as effects due to the recent history 21 of postsynaptic spiking and slow changes in postsynaptic excitability. Using paired spike 22recordings, we find that the model accurately describes the short-term dynamics of in vivo spike 23 transmission at a diverse set of identified and putative excitatory synapses, including a 24 thalamothalamic connection in mouse, a thalamocortical connection in a female rabbit, and an 25 auditory brainstem synapse in a female gerbil. We illustrate the utility of this modeling approach 26by showing how the spike transmission patterns captured by the model may be sufficient to account 27for stimulus-dependent differences in spike transmission in the auditory brainstem (endbulb of 28 Held). Finally, we apply this model to large-scale multi-electrode recordings to illustrate how such 29 an approach has the potential to reveal cell-type specific differences in spike transmission in vivo. 30Although short-term synaptic plasticity parameters estimated from ongoing pre-and postsynaptic 31 spiking are highly uncertain, our results are partially consistent with previous intracellular 32 observations in these synapses. 33Significance Statement (120 words) 34 Although synaptic dynamics have been extensively studied and modeled using intracellular 35 recordings of post-synaptic currents and potentials, inferring synaptic effects from extracellular 36 spiking is challenging. Whether or not a synaptic current contributes to postsynaptic spiking 37 depends not only on the amplitude of the current, but also on many other factors, including the 38 activity of other, typically unobserved, synapses, the overall excitability of the postsynaptic 39 neuron, and how recently the postsynaptic neuron has spiked. Here we developed a model that, 40using only observations of pre-and postsynaptic spiking, aims to describe the dynamics of in vivo 41 spike transmission by modeling both short-term synaptic plasticity and non-synaptic effects. This 42 approach may provide a novel description of fast, structured changes in spike transmission. 43