Motor and nonmotor domains in the monkey dentate.

Our concepts about the organization and functions of the cerebellum have changed substantially in the last 10 years. In recent studies, we used transneuronal virus tracing techniques to demonstrate that the output of the cerebellum of primates projects via the thalamus not only to its classical motor target, the primary motor cortex, but also to "nonmotor" cortical areas in the prefrontal and posterior parietal cortex. We found that dentate neurons projecting to different cortical areas originated from localized regions of the nucleus which we termed "output channels." To compare the locations of the output channels projecting to different cortical targets, we have created an unfolded map of the dentate. This unfolded map revealed that dentate output channels were segregated into spatially separate "motor" and "nonmotor" domains. The output channels in the motor domain exclusively targeted primary motor and premotor areas of the cerebral cortex. These channels were localized in the dorsal portion of the dentate. The output channels in the nonmotor domain projected to prefrontal and posterior parietal cortical areas. The nonmotor domain was confined to the ventral portion of the dentate. In recent studies, we defined a unique molecular marker, monoclonal antibody 8B3, which appears to differentially "recognize" these two domains. Taken together, our results suggest that dentate output is organized according to the functional capabilities of its cortical targets. This organization provides the dentate nucleus with the anatomical substrate to influence not only the control of movement, but also cognitive, higher-order executive and visuospatial functions.