The integrative function of the nervous system is predicated on the input-output properties of its individual neural elements. Although there are a number of empirical and analytical models of neuronal input-output behavior, none of them has general predictive value. The goal of the proposed research is to test and refine a computer model of a neuron that is based on the biophysical properties, is computationally tractable, and that accurately recreates neuronal input-output behavior over a wide range of conditions. The proposed work will primarily involve experimental measurement of the effects of synaptic and injected currents on the repetitive discharge of alpha motoneurons from the intact cat spinal cord in combination with computer simulation of the observed behaviors. The research design is based on the hypothesis that the response of a repetitively discharging neuron to synaptic input is determined by three processes: (1) the delivery of synaptic current to the soma (and the subsequent change in somatic membrane potential); (2) the interspike trajectory of somatic membrane potential; and (3) the interspike trajectory of voltage threshold. Project 1 is designed to examine the capacity of injected current transients to advance or delay spikes in repetitively discharging motoneurons in order to quantify variation in the voltage threshold for spike initiation. In Project 2, the effects of injected current transients on spike discharge will be compared to those of postsynaptic potentials from three identified sets of presynaptic neurons. In Project 3, a novel frequency matching paradigm will be used to compare the responses of real and model motoneurons to slowly-varying injected currents. This approach will be extended in Project 4 to an in vitro preparation of rat hypoglossal motoneurons in which long, stable intracellular recordings and more precise control of the extracellular environment are possible. In Project 5, neuromodulatory effects on neuronal input-output behavior will be studied by comparing motoneuron responses to selected inputs in four distinct preparations: intact barbiturate-anesthetized cats; unanesthetized decerebrate cats; decerebrate cats during stimulation of the mesencephalic locomotor region; and decerebrate-spinal cats with i.v. injection of serotonergic and noradrenergic precursors. The results of these studies will improve our understanding of the mechanisms underlying neuronal input-output behavior, and will also aid the interpretation of both human and chronic animal electrophysiological studies in which synaptic events are inferred from changes in motoneuron discharge.
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