Abstract
<jats:p>The development of a functional brain relies on the orchestration of the migration,differentiation and synaptic integration of each neuron with its specific inputs and output targets. The mechanisms controlling the proper timing of each of these processes in coordination with one another are poorly understood. Here we show that granule cells, the most numerous neuronal population in the mammalian brain, make immature synaptic contacts on their targets, the cerebellar Purkinje cells, when they reach the developing molecular layer and start their radial migration towards the internal granular layer where they will become innervated by their inputs, the mossy fibers. At this stage, granule cells have not completed their differentiation, but start expressing presynaptic markers, as well as a specific subtype of NMDA receptors. Chemogenetic manipulations show that decreased excitability of these differentiating granule cells prevents the maturation of their synapses on the Purkinje cell targets. Thus sensing of neuronal activity by differentiating granule cells coordinates the timing of their migration and input connectivity with the maturation of their synapses on their output targets. This coordination ensures the appropriate and timely transmission of sensorimotor information during brain development.</jats:p>