NEURONAL BASIS OF MOTOR LEARNING AND MEMORY IN BRAINSTEM AND CEREBELLAR CIRCUITS

New York University School Of Medicine, New York NY

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Abstract

The goal of this proposal is to delineate the brain stem and cerebellar circuits that produce horizontal eye movement and to determine the synaptic sites and mechanisms responsible for motor adaptation. Intra- and extracellular single cell recording combined with neuronal marking techniques have characterized most of the circuits responsible for producing vestibulo- and visuo-ocular reflexes. The actual elements of the neuronal circuits involved and the pharmacological properties of the various synaptic links are now well enough understood to propose models that specify the brain stem sites for adaptive plasticity and the roles of vestibulo-cerebellar Purkinje cells. These models provide the basis for four experimental aims. First, the afferent and efferent organization of eye movement related vestibular and prepositus neurons will be studied with the intra- and extracellular application of biocytin and fluorescent probes. The goal is to specify the morphological architecture necessary for all signal transformations. Second, vestibular and prepositus neuronal activity will be recorded during visuo-/vestibulo-motor adaptation to directly assess the causality of signal processing and specify cellular sites of plasticity. Third, the membrane properties and conductances of vestibular and prepositus neurons will be characterized to determine their roles in integration and motor adaptation. An in vivo pharmacological model will be implemented to examine motor plasticity. Fourth, the role of, and interaction between, the prepositus and inferior olivary mossy/climbing fiber cerebellar circuits will be studied by using electrical, chemical and surgical techniques. The overall objective of this project is to specify the neuronal circuitry both necessary and sufficient for visual and vestibular oculomotor performance, learning and memory. These studies address in cellular and pharmacological terms the inductive mechanisms employed in the acquisition and translation of sensory signals into adaptive motor behavior. The neurophysiological findings should be of significance for achieving a theoretical framework of motor co-ordination in other vertebrates while providing an accessible detailed neuronal organization in teleosts for future genetic and molecular studies of movement control.