Effects of Short-Term Synaptic Plasticity in Feedforward Inhibitory Circuits on Cerebellar Responses to Repetitive Sensory Input

Abstract

Short-term plasticity occurs at synapses throughout the cerebellum, raising the question of how such plasticity affects cerebellar processing in vivo. To address this issue, we recorded responses of molecular layer interneurons (MLIs), Purkinje cells, neurons of the cerebellar nuclei (CbN), and mossy fibers in the CbN, in awake head-fixed female mice. During short trains of air puffs applied to the whisker pad with intervals from 25 to 200 ms, the first puff generated brief suppressions of spike probability in Purkinje cells and brief elevations in all other cell types, resulting in coincident excitation and disinhibition of CbN cells and large whisker protractions. Later puffs evoked smaller whisks and smaller responses in all cells, with the strongest decrease in the CbN. The reduction resulted from facilitation of EPSCs from parallel fiber axons of granule cells decreasing net inhibition of individual Purkinje cells, and from activation of fewer MLIs reducing inhibition across the Purkinje population. Downstream, the decrease in Purkinje-mediated disinhibition, in conjunction with depression of excitatory mossy fiber-to-CbN pathways, reduced net excitation of CbN cells. Sensory-evoked responses were transient and effectively transmitted synaptically, but movement-related responses were prolonged and progressively cancelled at successive stages of the circuit. Moreover, many MLI, Purkinje, and CbN cells had bilateral receptive fields. In these cells, changing the stimulus location restored responsiveness and increased whisk magnitudes. Thus, several types of cerebellar neurons can report stimulus changes without specifying stimulus parameters, thereby serving as event detectors that can facilitate movement in response to altered sensory inputs.