Modeling short-term synaptic plasticity at the calyx of Held using in vivo-like stimulation patterns.

We measured synaptic responses to complex stimulus trains in the calyx of Held and used the data to test how well several vesicle-release models could capture the observed dynamics. We tested stimulation protocols consisting of Poisson-distributed activity with periodically changing mean frequencies, trains with constant inter spike intervals, and stimulus trains derived from in vivo responses to natural sounds. All stimuli were embedded in chronic background activity attempting to imitate the naturally occurring spontaneous activity in the auditory brain stem. We found that already the most basic model variant produced very good results, exhibiting very high correlation coefficients between the experimental data and the model predictions. None of the more complex model variants, which incorporated receptor desensitization, synaptic facilitation, and double-exponential recovery from depression, showed improved data-prediction matching accuracy. These findings are in contrast to previous modeling work performed in nonchronically active synapses, where the inclusion of additional physiological parameters into the modeling process tended to result in models with higher accuracy. Our findings suggest that the functional state of chronically active calyces may differ from the functional state of silent calyces and that this functional state of chronically active synapses can be described in relatively simple terms.