AnkriL+5-2015

Notes about [AnkriL+5-2015] 1.

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Lea Ankri, Zoé Husson, Katarzyna Pietrajtis, Rémi Proville, Clément Léna, Yosef Yarom, Stéphane Dieudonné, and Marylka Yoe Uusisaari. A novel inhibitory nucleo-cortical circuit controls cerebellar Golgi cell activity. eLife, 4:e06262, May 2015. URL: https://elifesciences.org/articles/06262, doi:10.7554/eLife.06262, Notes: AnkriL+5-2015.html (this file).

This paper shows that cerebellar nuclei (CN) neurons inhibit some Golgi cells.

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.

Other quotes from paper:

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Currently, the cerebellar cortex and the CN are known to interact through two circuits. The best known is the nucleo-olivary (NO) circuit (Apps and Garwicz, 2005; Apps and Hawkes, 2009; Chaumont et al., 2013), where the small GABAergic CN cells, subject to PN inhibition (Najac and Raman, 2015), project to the contralateral IO (Fredette and Mugnaini, 1991). This pathway regulates olivary activity (Chen et al., 2010; Bazzigaluppi et al., 2012; Chaumont et al., 2013; Lefler et al., 2014) and thereby complex spike activity in the PNs and cerebellar cortical plasticity (Hansel and Linden, 2000; Coesmans et al., 2004; Bengtsson and Hesslow, 2006; Medina and Lisberger, 2008).

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 also Tolbert et al., 1976, 1977, 1978; Ha´mori et al., 1980; Payne, 1983). The functional significance of this excitatory nucleo-cortical (eNC) pathway, loosely following the modular arrangement of the cerebellum (Dietrichs and Walberg, 1979; Gould, 1979; Haines and Pearson, 1979; Tolbert and Bantli, 1979; Buisseret-Delmas, 1988; Provini et al., 1998; Ruigrok, 2010 ; reviewed by Houck and Person, 2013), is likely related to efference copying of motor commands to the cerebellar cortex (Sommer and Wurtz, 2008; Houck and Person, 2015).

In addition to the pathways linking the CN with the cerebellar cortex mentioned above, evidence has occasionally emerged for an inhibitory nucleo-cortical (iNC) pathway. GABAergic neurons have been shown to be labeled in the CN by retrograde tracing from the cerebellar cortex (Batini et al., 1989), and nucleo-cortical terminals with non-glutamatergic ultrastructural features have been found to contact putative Golgi cell dendrites (Tolbert et al., 1980). More recently, it was demonstrated that GlyT2-expressing CN neurons extend axons toward the cerebellar cortex (Uusisaari and Kno¨pfel, 2010), suggesting that the iNC pathway might be identifiable by its glycinergic phenotype. While the iNC projection is likely to have significant impact on cerebellar computation, its postsynaptic targets and its functional organization remain unknown.