IL1RAPL1 controls inhibitory networks during cerebellar development in mice
European Journal of Neuroscience. 2009-10-01; 30(8): 1476-1486
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1. Eur J Neurosci. 2009 Oct;30(8):1476-86. doi: 10.1111/j.1460-9568.2009.06975.x.
Epub 2009 Oct 7.
IL1RAPL1 controls inhibitory networks during cerebellar development in mice.
Gambino F(1), Kneib M, Pavlowsky A, Skala H, Heitz S, Vitale N, Poulain B,
Khelfaoui M, Chelly J, Billuart P, Humeau Y.
(1)Institut des Neurosciences Cellulaires et Intégratives, UPR3212, Centre
National de la Recherche Scientifique, 67084 Strasbourg, France.
Abnormalities in the formation and function of cerebellar circuitry potentially
contribute to cognitive deficits in humans. In the adult, the activity of the
sole output neurons of the cerebellar cortex – the Purkinje cells (PCs) – is
shaped by the balance of activity between local excitatory and inhibitory
circuits. However, how this balance is established during development remains
poorly understood. Here, we investigate the role of interleukin-1 receptor
accessory protein-like 1 (IL1RAPL1), a protein linked to cognitive function which
interacts with neuronal calcium sensor 1 (NCS-1) in the development of mouse
cerebellum. Using Il1rapl1-deficient mice, we found that absence of IL1RAPL1
causes a transient disinhibition of deep cerebellar nuclei neurons between
postnatal days 10 and 14 (P10/P14). Upstream, in the cerebellar cortex, we found
developmental perturbations in the activity level of molecular layer interneurons
(MLIs), resulting in the premature appearance of giant GABAA-mediated inhibitory
post-synaptic currents capable of silencing PCs. Examination of feed-forward
recruitment of MLIs by parallel fibres shows that during this P10/P14 time
window, MLIs were more responsive to incoming excitatory drive. Thus, we conclude
that IL1RAPL1 exerts a key function during cerebellar development in establishing
local excitation/inhibition balance.
PMID: 19811529 [Indexed for MEDLINE]