The regulation of voluntary motor activity is presumed to involve brain pathways in the central nervous system that link the cerebral cortex and cerebellum. Clearly one of the most important of these pathways is the vast system of cortical axons that transmit information to the cerebellum via an obligatory synapse in the basilar pontine nuclei (BPN). However, recent work from this laboratory has suggested that the BPN might be more properly regarded as an integrating station for a wide variety of signals which are ultimately directed at the cerebellum. This notion is supported by (a) the presence of a population of GABA-ergic neurons in the BPN, (b) afferent projections from an unusually diverse aggregate of cell groups throughout the brain and spinal cord, as well as (c) feedback circuits from the cerebellum itself. Because of an interest in the regulation of voluntary motor behavior and the obvious involvement of such systems in a variety of neurological disorders ranging from developmental insults such as cerebral palsy to cerebral stroke, we propose to undertake several correlated anatomical and physiological studies which are designed to provide some degree of understanding of how the BPN might be involved in the control of motor behavior. More specifically, through the use of intracellular recording and the subsequent filling of the identified cell with HRP, we hope to resolve two long-standing fundamental questions pertaining to BPN circuitry; namely, are intrinsic, local circuit type neurons present in the BPN and , secondly, do some of the projection neurons give rise to axonal branches within the pontine gray before coursing into the cerebellum? In general, our experiments will represent an even mix of anatomy and physiology in the hope of clarifying not only the structure but also the functional parameters of BPN neurons. Additionally, our efforts will focus on a determination of the functional role played by the recently discovered GABA afferent projections to the BPN along with electron microscopic immunochemical studies designed to identify serotonergic, noradrenergic and glutaminergic synaptic boutons in the BPN. Taken together, the studies in this proposal will answer several long-standing questions regarding the intrinsic circuitry of the BPN and initiate much needed electrophysiological studies of BPN neurons and the recently discovered GABA-ergic afferent systems. Observations from these studies should provide fundamental insight into the actual functional role of the BPN as a processing center for various inputs directed ultimately at the cerebellum.
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