The Role of Interneurons in Shaping Purkinje Cell Responses in the Cerebellar Cortex

Abstract

The well established anatomy of the cerebellar cortex has led to suggestions that cerebellar molecular layer interneurons laterally inhibit Purkinje cells. In support of the anatomical predictions, on-beam excitation and off-beam inhibition of Purkinje cells have been shown to occur when the surface of the cerebellum is electrically excited. Patchy excitation of Purkinje cells with flanking inhibition of sagittally oriented Purkinje cells have also been demonstrated following peripheral stimulation in vivo. To extend these observations, we mapped the functional connectivity between granule cells, molecular layer interneurons, and Purkinje cells in rats. Patches of granule cells were asynchronously activated by photostimulation to mimic their excitation by a mossy fiber as it occurs in vivo. We found with remarkable consistency that, in the sagittal orientation, granule cells elicit a stereotypic set of responses. Granule cells immediately underneath a Purkinje cell provide pure excitation. Granule cells positioned 340-400 μm laterally provided pure inhibition, consistent with the lateral inhibition proposed earlier. The net effect of exciting granule cells in between these two extremes was to provide a systematic change in the response of Purkinje cells, from net excitation to net inhibition moving laterally from the Purkinje cell. In contrast to the sagittal orientation, in the coronal orientation the organization of Purkinje cell responses with granule cell activation was remarkably different. Independent of the location of granule cells, within the 480 μm lateral distance examined, molecular layer interneurons reduced the strength of granule cell inputs to Purkinje cells to a comparable extent.