Granule Cell Ascending Axon Excitatory Synapses onto Golgi Cells Implement a Potent Feedback Circuit in the Cerebellar Granular Layer

The function of inhibitory interneurons within brain microcircuits depends critically on the nature and properties of their excitatory synaptic drive. Golgi cells (GoCs) of the cerebellum inhibit cerebellar granule cells (GrCs) and are driven both by feedforward mossy fiber (mf) and feedback GrC excitation. Here, we have characterized GrC inputs to GoCs in rats and mice. We show that, during sustainedmf discharge, synapses from local GrCs contribute equivalent charge to GoCs as mfsynapses, arguing for the importance of the feedback inhibition. Previous studies predictedthat GrC-GoC synapses occur predominantly between parallelfibers (pfs) and apical GoC dendrites in the molecular layer (ML). By combining EM and Ca2 imaging, we now demonstrate the presence of functional synaptic contacts between ascending axons (aa) of GrCs and basolateral dendrites of GoCs inthe granular layer (GL). Immunohistochemical quantification estimatesthese contactsto be400 per GoC.Using Ca2imagingtoidentify synapticinputs,we showthat EPSCsfromaaandmfcontacts in basolateral dendrites display similarly fast kinetics, whereas pf inputs in the ML exhibit markedly slower kinetics as they undergo strong filtering by apical dendrites. We estimate that approximately half of the local GrC contacts generate fast EPSCs, indicating their basolateral location inthe GL.We concludethat GrCs,throughtheiraacontacts onto proximal GoC dendrites, define a powerfulfeedback inhibitory circuit in the GL.