title: Control of cerebellar granule cell output by sensory-evoked Golgi cell inhibition.
abstract: Classical feed-forward inhibition involves an excitation-inhibition sequence that enhances the temporal precision of neuronal responses by narrowing the window for synaptic integration. In the input layer of the cerebellum, feed-forward inhibition is thought to preserve the temporal fidelity of granule cell spikes during mossy fiber stimulation. Although this classical feed-forward inhibitory circuit has been demonstrated in vitro, the extent to which inhibition shapes granule cell sensory responses in vivo remains unresolved. Here we combined whole-cell patch-clamp recordings in vivo and dynamic clamp recordings in vitro to directly assess the impact of Golgi cell inhibition on sensory information transmission in the granule cell layer of the cerebellum. We show that the majority of granule cells in Crus II of the cerebrocerebellum receive sensory-evoked phasic and spillover inhibition prior to mossy fiber excitation. This preceding inhibition reduces granule cell excitability and sensory-evoked spike precision, but enhances sensory response reproducibility across the granule cell population. Our findings suggest that neighboring granule cells and Golgi cells can receive segregated and functionally distinct mossy fiber inputs, enabling Golgi cells to regulate the size and reproducibility of sensory responses.
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom ian.duguid@ed.ac.uk m.hausser@ucl.ac.uk.
authors.forename: Ian
authors.initials: I
authors.lastname: Duguid
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Tiago
authors.initials: T
authors.lastname: Branco
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Paul
authors.initials: P
authors.lastname: Chadderton
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Arlt
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
authors.forename: Kate
authors.initials: K
authors.lastname: Powell
authors.affiliation: Wolfson Institute for Biomedical Research and Department of Neuroscience, Physiology, and Pharmacology, University College London, London WC1E 6BT, United Kingdom ian.duguid@ed.ac.uk m.hausser@ucl.ac.uk.
authors.forename: Michael
authors.initials: M
authors.lastname: Häusser
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000502:physiology*; D003594:Cytoplasmic Granules / Q000502:physiology*; D006056:Golgi Apparatus / Q000502:physiology*; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
keywords: Golgi cells; cerebellum; granule cells; inhibition; synaptic integration