This proposal aims to determine the functional significance of synaptic processing in the deep cerebellar nuclei (DCN), which provide the only output from cerebellum. Projection neurons in the DCN are controlled by excitatory input from the brainstem and the cerebral cortex, and by inhibitory input from cerebellar cortical Purkinje cells. The Purkinje cells themselves are controlled by the same excitatory inputs that are also received as collaterals by the DCN directly. This connectivity thus allows individual DCN projection neurons to compare the same signal before and after processing by the cerebellar cortex. The ensuing spike modulation of DCN neurons is believed to directly correspond to motor command signals aiding in movement coordination. We will combine intracellular and extracellular recordings in vivo and in vitro from the rat with computer modeling of this system to gain a better understanding of the important confluence of signals in the DCN. We will test the hypothesis that DCN output commands can be activated by excitatory inputs from outside the cerebellum. We will test the hypothesis that DCN output commands can also be generated by disinhibition due to pauses in spiking of groups of Purkinje cells. We will furthermore test the hypothesis that intrinsic active properties of DCN neurons make an important contribution to signal generation. Specifically we will determine whether DCN neurons may show bistability leading to a change in the time course of spike rate changes in the cerebellum. Rescaling the temporal properties of spike rate changes in the input to suit the control of muscle activity may be a fundamental function of the DCN. These studies are expected to generate important insights into cerebellar function and the mechanisms underlying cerebellar movement disorders. ? ?
