CONTROL OF OSCILLATORY MEMBRANE POTENTIALS IN MOTOR NEURONS

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During locomotion, rhythmic bursts of action potentials in motoneurons depend upon underlying oscillations in membrane potential (Vm). The proposed study will test the hypothesis that N-methyl-D-aspartic acid (NMDA) receptors on spinal motoneurons control the incidence and magnitude of such oscillations in mammals. Two specific objectives are to determine if NMDA receptors: 1) must be activated before Vm oscillations are sufficient to support rhythmic firing; and 2) regulate the rhythmogenic effects of L-DOPA and serotonin on motoneurons. Intracellular recordings from neonatal mouse motoneurons will be obtained from acute lumbosacral explants as well as from organotypic (long-term slice) cocultures of lumbar tissue with muscle. A third objective is to determine if motoneurons in cocultures resemble those in acute spinal explants. This will be accomplished by comparing both physiological and morphological data across preparations. Motoneurons in both preparations will be injected with HRP, so comprehensive morphometric analyses can be obtained. The new information on the control of Vm oscillations in motoneurons will significantly advance our understanding of how motor rhythms are expressed. If there is a sufficient resemblance in motoneuron function and structure across preparations, a valuable new in vitro system will have been established for future, more detailed studies. The fourth objective of this work is of course to recruit and train minority students in biomedical research. The mission Texas Woman's University has for training women and minorities means that the proposed work would carry a much needed impact upon science education in Texas.