| First Author | Gambino F | Year | 2009 |
| Journal | Eur J Neurosci | Volume | 30 |
| Issue | 8 | Pages | 1476-86 |
| PubMed ID | 19811529 | Mgi Jnum | J:155437 |
| Mgi Id | MGI:4413653 | Doi | 10.1111/j.1460-9568.2009.06975.x |
| Citation | Gambino F, et al. (2009) IL1RAPL1 controls inhibitory networks during cerebellar development in mice. Eur J Neurosci 30(8):1476-86 |
| abstractText | 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. |
