Granule cell ascending axon excitatory synapses onto Golgi cells implement a potent feedback circuit in the cerebellar granular layer

Elisabetta Cesana, Katarzyna Pietrajtis, Céline Bidoret, Philippe Isope, Egidio D'Angelo, Stéphane Dieudonné, Lia Forti

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30 Citations (Scopus)

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 Ca2+ 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 Ca2+ 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.

Original languageEnglish
Pages (from-to)12430-12446
Number of pages17
JournalJournal of Neuroscience
Volume33
Issue number30
DOIs
Publication statusPublished - 2013

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Synapses
Axons
Dendrites
Interneurons
Cerebellum
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

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Granule cell ascending axon excitatory synapses onto Golgi cells implement a potent feedback circuit in the cerebellar granular layer. / Cesana, Elisabetta; Pietrajtis, Katarzyna; Bidoret, Céline; Isope, Philippe; D'Angelo, Egidio; Dieudonné, Stéphane; Forti, Lia.

In: Journal of Neuroscience, Vol. 33, No. 30, 2013, p. 12430-12446.

Research output: Contribution to journalArticle

Cesana, Elisabetta ; Pietrajtis, Katarzyna ; Bidoret, Céline ; Isope, Philippe ; D'Angelo, Egidio ; Dieudonné, Stéphane ; Forti, Lia. / Granule cell ascending axon excitatory synapses onto Golgi cells implement a potent feedback circuit in the cerebellar granular layer. In: Journal of Neuroscience. 2013 ; Vol. 33, No. 30. pp. 12430-12446.
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