Maturation of Purkinje cell firing properties relies on granule cell neurogenesis

Abstract

Preterm infants that suffer cerebellar insults often develop motor disorders and cognitive difficulty. Granule cells are especially vulnerable, and they likely instigate disease by impairing the function of Purkinje cells. Here, we use regional genetic manipulations and in vivo electrophysiology to test whether granule cells help establish the firing properties of Purkinje cells during postnatal mouse development. We generated mice that lack granule cell neurogenesis and tracked the structural and functional consequences on Purkinje cells in these agranular pups. We reveal that Purkinje cells fail to acquire their typical connectivity and morphology, and the formation of characteristic Purkinje cell firing patterns is delayed by one week. We also show that the agranular pups have impaired motor behaviors and vocal skills. These data argue that granule cell neurogenesis sets the maturation time window for Purkinje cell function and refines cerebellar-dependent behaviors.