Lack of coordination results not only from lesions of structures such as the cerebellum, which ar generally thought to play an important role in controlling movement, but also from compromise of structures such as the dorsal columns and their relay, the dorsal column nuclei, that provide sensory information to the cerebellum. Information from the dorsal column nuclei reaches the cerebellum through a number of projections, most of which arise from widely scattered neurons that cannot be subjected to detailed experimental evaluation. Work from this laboratory has shown, however, that in cat the connection from the gracile portion of the dorsal column nuclei to the dorsal accessory subdivision of the inferior olive (DAO) constitutes not only a substantial source of somatosensory information for the cerebellum but one amenable to experimental manipulation. The DAO projection neurons in the gracile nucleus appear to preferentially signal contracts with external objects that occur at unexpected times during movement. The proposed electron microscopic experiments will investigate the anatomical substrates that underlie such signalling. The first experiment will determine the synaptic mechanisms through which the dorsal column fibers activated by external contact might interact with DAO projection neurons in the gracile nucleus. The DAO projection neurons will be identified with a retrograde tracer; synaptic inputs from the dorsal columns will be labeled with degeneration. Inhibitory elements that might regulate responsiveness of DAO projection neurons to these inputs will be identified using antibodies to the neurotransmitter GABA. The second experiment seeks to determine how inhibition of the DAO projection neurons might be achieved. This will be done by evaluating whether, and at what sites, putative GABAergic neurons adjacent to DAO projection neurons receive inputs that might signal the occurrence of either motor commands (the cerebral cortex) or contact with external objects (the dorsal columns). The data collected from these and other experiments in this laboratory will help determine how compromise of the dorsal columns and dorsal column nuclei might contribute to production of motor deficits and, ultimately, to a greater understanding of how sensory information is used to generate coordinated movement.
