The work proposed herein is towards the development of a comprehensive model for the analysis of signal transmission between the mammalian sensory receptor hair cell-afferent synapse and associated afferent fiber. A description is formulated in terms of interacting stochastic processes which are direct analogues of the physiological mechanisms of the mechanical/electrical operation of the synapse-afferent complex: vesicle recycle to synaptic body, vesicle transfer from synaptic body to docking sites, vesicle release via exocytosis, excitatory post-synaptic potential generation, and action potential generation. The model of the receptor synapse is based on the current experimental understanding of its molecular mechanisms of exocytosis allowing for a comprehensive study of the pre- and post-synaptic regulation of transmission in a systematic way. Such a model provides the vehicle for synthesis and prediction of the complex nonstationary responses of the synapse-afferent complex. A testimony to the model is in its predictive power. On the post-synaptic side, it predicts a direct link between the postsynaptic recovered discharge properties with the interaction between synaptic conductance and post-synaptic threshold voltage dynamics. It also predicts that the long- time constants associated with post-synaptic recovered discharge are linked to a yet to be identified long-time constant hyperpolarization in the post-synaptic afferent membrane, and it predicts the existence of the nonmonotonic discharge peak seen by various investigators in recovered response histograms at absolute dead-time. Simultaneously the model predicts a regime over which the Siebert/Gaumond discharge intensity product model holds. On the pre-synaptic side, the model predicts how the roles played by the synaptic stochastic processes, vesicle transfer from synaptic body to docking sites and vesicle exocytosis rate, determine the complex recovery and adaption rates observed during stimulation. The framework in which the receptor cell synapse is defined is general enough that it can be extended to more complex synaptic systems, such as that seen in the acousticolateral system in fish. This will allow for the direct modeling of afferents with multiple synapses and complex dendritic trees, revealing the mechanisms by which synaptic morphology directly determines afferent response dynamics. A model of synaptic transduction also provides researchers studying the regularity properties of neurons in the cochlear nucleus with realistic inputs with which to understand processing at higher levels. The major contribution is to provide an organized setting in which hypotheses concerning the receptor-synapse- afferent system can be tested. Viewing the synapse-afferent system as the concatenation of multiple interacting random processes, it allows for the direct inference from action potential data of the mechanisms of receptor cell transduction, inferences which are free from the distortive effects of pre- and post-synaptic adaptation. This can become a major tool for formulating questions about the roles played by the various components of the synapse and associated afferent fibers in encoding sensory information.
| Schmich, R M; Miller, M I (1997) Stochastic threshold characterization of the intensity of active channel dynamical action potential generation. J Neurophysiol 78:2616-30 |
| Miller, M I; Wang, J (1993) A new stochastic model for auditory-nerve discharge. J Acoust Soc Am 94:2093-107 |
| Mark, K E; Miller, M I (1992) Bayesian model selection and minimum description length estimation of auditory-nerve discharge rates. J Acoust Soc Am 91:989-1002 |
