A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity

Lea Ankri,Zoé Husson,Stéphane Dieudonné,Yosef Yarom,Katarzyna Pietrajtis,Clément Léna,Rémi Proville,Marylka Yoe Uusisaari

doi:10.7554/elife.06262

Lea Ankri, Zoé Husson + Show 6 more

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https://doi.org/10.7554/elife.06262

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Abstract

The cerebellum, a crucial center for motor coordination, is composed of a cortex and several nuclei. The main mode of interaction between these two parts is considered to be formed by the inhibitory control of the nuclei by cortical Purkinje neurons. We now amend this view by showing that inhibitory GABA-glycinergic neurons of the cerebellar nuclei (CN) project profusely into the cerebellar cortex, where they make synaptic contacts on a GABAergic subpopulation of cerebellar Golgi cells. These spontaneously firing Golgi cells are inhibited by optogenetic activation of the inhibitory nucleo-cortical fibers both in vitro and in vivo. Our data suggest that the CN may contribute to the functional recruitment of the cerebellar cortex by decreasing Golgi cell inhibition onto granule cells.

Highlights

The cerebellum plays a key role in the fine temporal control of posture and movements as well as in cognitive processes (Ito, 1993; Leiner et al, 1993)
As the functional significance of the inhibitory nucleo-cortical (iNC) pathway is likely to be amplified by the high divergence of Golgi cells, which target thousands of granule cell (GrC) (Hamori and Somogyi, 1983; Jakab and Hamori, 1988; Andersen et al, 1992; Korbo et al, 1993), as well as the remarkable mediolateral extent of the iNC axons, the cerebellar nuclei (CN) might play a key role in the regulation of the information flow through the granule cell layer (GrCL)
We reveal an iNC pathway in the cerebellum

Summary

Introduction

The cerebellum plays a key role in the fine temporal control of posture and movements as well as in cognitive processes (Ito, 1993; Leiner et al, 1993). A less-known nucleo-cortical circuit is formed by the glutamatergic neurons of the CN which, in addition to projecting to various premotor and associative regions of the brain (Tsukahara and Bando, 1970; Asanuma et al, 1980; Angaut et al, 1985; Sultan et al, 2012; Ruigrok and Teune, 2014), send axonal collaterals to the cerebellar granule cell layer (GrCL; Houck and Person, 2015) These collateral fibers form MF-like terminals contacting granule cell (GrC) and Golgi cell dendrites (see Tolbert et al, 1976, 1977, 1978; Hamori et al, 1980; Payne, 1983). As the functional significance of the iNC pathway is likely to be amplified by the high divergence of Golgi cells, which target thousands of GrCs (Hamori and Somogyi, 1983; Jakab and Hamori, 1988; Andersen et al, 1992; Korbo et al, 1993), as well as the remarkable mediolateral extent of the iNC axons, the CN might play a key role in the regulation of the information flow through the GrCL

Results

Discussion

Materials and methods