MECHANISMS OF MAMMALIAN NEURONAL INTEGRATION

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DESCRIPTION (adapted from applicant's abstract) The continuing long term goal of this project is to understand the intrinsic mechanisms and synaptology underlying the integrative functions of spinal cord neurons involved in the control of locomotion in mammals. It is now accepted that dendrites, far from being passive participants in neuronal function, possess intrinsic active properties that can significantly influence the transmission of information. Therefore the dendrites, as well as the soma, likely display a broad complement of voltage-gated ion channels that underlie these active properties. Because the distribution of voltage-gated channels is a critical factor for normal integrative function, and may also play a role in the reaction of neurons to injury, the investigator seeks to understand the subcellular organization of these channels, particularly in the soma and dendrites. They hypothesize that both the expression and subcellular localization of voltage-gated channels in spinal neurons are type specific and, insofar as the function of cloned channel subunits is known, are correlated with specific aspects of neuronal firing and/or with excitability changes that occur in response to axotomy. They will use novel combinations of electrophysiological and immunohistochemical approaches 1) to demonstrate the expression and subcellular localization of voltage gated ion channels in various physiologically identified classes of spinal neuron in vivo, and to correlate ion channel expression and distribution patterns with known membrane and firing properties of the neurons. They will also 2) determine whether or not certain classes of voltage gated ion channels are associated with or are adjacent to certain types of synapses, and 3) determine how the expression and distribution of voltage gated ions channels is altered in axotomized motoneurons to test the hypothesis that the response to axotomy will involve a redistribution of voltage gated ion channels to the dendrites. By allowing them to integrate knowledge of voltage gated ion channel distribution with their knowledge of neuron structure, synaptology, and receptor organization, the results will provide unprecedented information and insight into the molecular and structural basis of neuronal properties in segmental motoneurons, interneurons, and projection neurons.