This program grant continues our study of neural mechanisms controlling motor performance and homeostasis. Control of movements nad homeostatic functions represents the major set of actions of the central nervous system (CNS). Understanding the CNS mechanisms that underlie these fundamental control systems is of great importance as a basic question in neurobiology and also for the understanding and eventual treatment of many diseases. In recent years neuroscientists have made rapid progress in elucidating the molecular and cellular mechanisms that underlie nervous system functioning. New neuroanatomical techniques have also revealed many of the connections that subserve CNS functions and have provided information about the neural transmitters that they employ. The biggest gap in our understanding of integrative actions of the CNS is the relationship of these pathways and mechanisms to function in a behavioral context. To help fill this gap, we are proposing 8 projects whose goal is to determine how the CNS integrates single neuron activity to generate actual behavior. Peterson proposes to study the control of head movement by vestibulospinal and reticulospinal systems. McCrimmon will investigate the electrophysiology and neuropharmacology of pathways that regulate respiration. McKenna will study brainstem control of sexual reflexes. Rymer will investigate the role of spinal circuits in generating movement synergies. Baker will study the role o the vestibulocerebellum in plastic, adaptive changes in the vestibuloocular reflex. Slate will study the biophysics and pharmacology of plasticity in the cerebellar cortex. Hockberger will study the pacemaker properties of cerebellar Purkinje cells. Houk will study neural substrates of motor programs in the cerebello-rubrospinal system. These eight projects center around four overlapping themes: 1) Brainstem control of patterned motor outputs, 2) organization of motor patterns, 3) cerebellar circuits for sensorimotor control and 4) mechanisms of motor learning. Collectively these four themes represent a concerted attack on some of the most challenging problems of integrative neuroscience. Core support is requested for computer, instrumentation, histology and administration in order to provide the projects with state-of-the-art facilities and support as required to accomplish the scientific aims of this proposal. The unique value of this Program Project lies in the extensive interaction between members of the Program Project group and in the way in which the eight projects and four core facilities serve as magnet to focus their extensive research activities into a concerted effort to confront neural systems problems in novel and effective ways.
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