Excitation and inhibition delays within a feedforward inhibitory pathway modulate cerebellar Purkinje cell output in mice

Abstract

The cerebellar cortex computes sensorimotor information from many brain areas through a feedforward inhibitory (FFI) microcircuit between the input stage, the granule cell layer, and the output stage, the Purkinje cells. While in other brain areas FFI underlies a precise excitation vs inhibition temporal correlation, recent findings in the cerebellum highlighted more complex behaviors at the granule cell (GC) - molecular layer interneuron (MLI) - Purkinje cell (PC) FFI pathway. To dissect the temporal organization of the cerebellar FFI pathway, we combined ex vivo patch clamp recordings of PCs with a viral-based strategy to express Channelrhodopsin2 in a subset of mossy fibers (MFs), a major excitatory input to GCs. We show that light-mediated MF activation elicits excitatory and inhibitory currents in PCs with a wide range of temporal delays. Furthermore, in many recordings, excitation and inhibition were initiated by different groups of GCs, expanding PCs synaptic temporal integration. Using a computational model of the FFI pathway we demonstrated that this temporal expansion could strongly influence how PCs integrate MF inputs. Our findings suggest that MF inputs are also encoded by specific delays between excitation and inhibition in PCs.