Model-founded explorations of the roles of molecular layer inhibition in regulating Purkinje cell responses in cerebellar cortex: more trouble for the beam hypothesis

摘要

For most of the last 50 years, the functional interpretation for inhibition in cerebellar cortical circuitry has been dominated by the relatively simple notion that excitatory and inhibitory dendritic inputs sum, and if that sum crosses threshold at the soma the Purkinje cell generates an action potential. Thus, inhibition has traditionally been relegated to a role of sculpting, restricting, or blocking excitation. At the level of networks, this relatively simply notion is manifest in mechanisms like ‘surround inhibition’ which is purported to ‘shape’ or ‘tune’ excitatory neuronal responses. In the cerebellum, where all cell types except one (the granule cell) are inhibitory, these assumptions regarding the role of inhibition continue to dominate. Based on our recent series of modeling and experimental studies, we now suspect that inhibition may play a much more complex, subtle and central role in the physiological and functional organization of cerebellar cortex. This paper outlines how model-based studies are changing our thinking about the role of feed-forward molecular layer inhibition in the cerebellar cortex. The results not only have important implications for continuing efforts to understand what the cerebellum computes, but might also reveal important features of the evolution of this large and quintessentially vertebrate brain structure.