CENTRAL RHYTHMOGENESIS AND BEHAVIOR

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Graceful and skilled movements require the function of the highly parallel and distributed projection of the inferior olive to the cerebellum. The hallmark of olivo-cerebellar dysfunction is the inability to perform sequences of skilled movement requiring simultaneous actions of many muscles on both sides of the body. This proposal attempts to understand how rhythmic activity within the inferior olive facilitates the organization and coordination of skilled movement. These experiments will employ in vivo multi-electrode recording of Purkinje cell complex-spike activity while rats perform a series of behavioral tasks in order to elucidate how muscular synergies are permitted to evolve by this parallel-processing system. Behaviors under study will be skilled and goal-directed movements of the tongue. Rats will be conditioned to protrude their tongue in a variety of ways under discrete-trial and free operant procedures, to make spatial discriminations in order to guide movement direction, and to perform simultaneous and skilled movements of the forelimb and tongue. Electromyographic recording of the activity of three tongue muscles during multi-electrode neural recording will provide an opportunity to determine whether subpopulations of olivary neurons with characteristic resonant frequencies selectively modulate specific muscle groups during skilled movement. Rhythmic activity of the olivo-cerebellar system will be manipulated by injecting the neurotoxin apamin into the inferior olive, in order to determine whether disrupting the rhythm of olivary activity disrupts muscle synergies required for skilled movement. Finally, simultaneous and purposeful movements of the tongue and forelimb during multi-electrode recording of Purkinje cell complex spike activity will provide insight into how muscular synergies manifested in parallel are modulated by a parallel-processing network in the brain whose function is of the utmost importance for fluid and graceful movement.