title: Granule cell ascending axon excitatory synapses onto Golgi cells implement a potent feedback circuit in the cerebellar granular layer.
abstract: 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 sustained mf discharge, synapses from local GrCs contribute equivalent charge to GoCs as mf synapses, arguing for the importance of the feedback inhibition. Previous studies predicted that GrC-GoC synapses occur predominantly between parallel fibers (pfs) and apical GoC dendrites in the molecular layer (ML). By combining EM and Ca(2+) imaging, we now demonstrate the presence of functional synaptic contacts between ascending axons (aa) of GrCs and basolateral dendrites of GoCs in the granular layer (GL). Immunohistochemical quantification estimates these contacts to be ∼400 per GoC. Using Ca(2+) imaging to identify synaptic inputs, we show that EPSCs from aa and mf contacts 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 in the GL. We conclude that GrCs, through their aa contacts onto proximal GoC dendrites, define a powerful feedback inhibitory circuit in the GL.
authors.affiliation: Brain Connectivity Center, Istituto di Ricovero e Cura a Carattere Scientifico C. Mondino, 27100 Pavia, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Cesana
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Pietrajtis
authors.forename: Céline
authors.initials: C
authors.lastname: Bidoret
authors.forename: Philippe
authors.initials: P
authors.lastname: Isope
authors.forename: Egidio
authors.initials: E
authors.lastname: D'Angelo
authors.forename: Stéphane
authors.initials: S
authors.lastname: Dieudonné
authors.forename: Lia
authors.initials: L
authors.lastname: Forti
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000818:Animals; D001369:Axons / Q000502:physiology* / Q000648:ultrastructure; D002118:Calcium / Q000378:metabolism; D002531:Cerebellum / Q000166:cytology* / Q000502:physiology*; D003712:Dendrites / Q000502:physiology / Q000648:ultrastructure; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D025461:Feedback, Physiological / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D007395:Interneurons / Q000502:physiology / Q000648:ultrastructure; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000502:physiology / Q000648:ultrastructure; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D013569:Synapses / Q000502:physiology*
chemical_list: D049452:Green Fluorescent Proteins; D002118:Calcium