Research Project
6126182
The basal ganglia and cerebellum are major subcortical nuclei that have long been regarded as critical to the generation and control of movement. A major structural feature of basal ganglia and cerebellar circuits is their participation in multiple open and closed loops with the cerebral cortex. In the past, basal ganglia and cerebellar output was thought to terminate in a single region of the thalamus and influence a single cortical area, the primary motor cortex. It is now becoming increasingly clear that the output of these circuits is much more widespread than previously suspected. Recently, we used a new tracing technique, retrograde transneuronal transport of herpes simplex virus type 1, to examine some basal ganglia and cerebellar projections to the cerebral cortex. Our results indicated that the output from the basal ganglia and cerebellum directly influences prefrontal areas of cortex, as well as motor areas. We have proposed that the projection to prefrontal cortex provides a means for the basal ganglia and cerebellum to influence frontal lobe functions such as working memory, rule-based learning and the planning of future behavior. We now propose to use the same technique to examine the extent of basal ganglia and cerebellar projections to temporal posterior parietal, and cingulate cortex. Connections with these cortical areas would provide the anatomical substrate for basal ganglia and cerebellar participation in aspects of perception, attention and other higher order cognitive processes. Indeed, damage to these circuits or alterations in their development have been thought to be the anatomical basis of a number of symptoms associated with mental disorders such as schizophrenia, autism and obsessive-compulsive disorder. Thus, the results of the proposed experiments could have important implications for concepts regarding basal ganglia and cerebellar contributions to normal and abnormal behavior.
