For 150 years the cerebellum has been assumed to be primarily involved in regulating movement. In addition, most functional models of cerebellar movement control are based on a 100 year old understanding of the anatomical and physiological organization of this structure. Over the last 10 years, however, evidence has accumulated that the cerebellum may be involved in much more than just movement control. Paralleling this rather dramatic change in thinking about overall cerebellar function, recent experimental results also suggest that the standard functional interpretation of the organization of cerebellar circuits may also require significant revision. Specifically, most cerebellar models and theories are based on the assumption that the 150,000 parallel fiber excitatory synaptic inputs provided each cerebellar Purkinje cell (the largest excitatory synaptic convergence for any cell in the mammalian nervous system) directly drive the generation of Purkinje cell action potentials, i.e., their output. Accumulating experimental and modeling evidence suggests that this is not the case. The research supported here uses a combination of realistic computer modeling techniques, electrophysiology, and anatomy to better understand the apparent lack of direct excitatory influence of this massive synaptic convergence on Purkinje cells in the rat. In particular, this research is focused on the functional role played by cerebellar cortical inhibitory neurons, which have largely been overlooked, in current theories of cerebellar function. The specific hypothesis tested is that inhibition in the so-called molecular layer of the cerebellum dynamically counteracts the excitatory effect of the parallel fibers, turning the parallel fiber / molecular layer inhibitory system into a modulatory, rather than a direct driving, influence. The results are expected to provide a new foundation for our rapidly expanding and evolving understanding of the functional organization of the cerebellar cortical network, and accordingly a new foundation for considering the general role of the cerebellum in the mammalian brain. The research will also provide research involvement for individuals from groups typically underrepresented in science.
