title: IL1RAPL1 controls inhibitory networks during cerebellar development in mice.
abstract: 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.
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives, UPR3212, Centre National de la Recherche Scientifique, 67084 Strasbourg, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Gambino
authors.forename: Marie
authors.initials: M
authors.lastname: Kneib
authors.forename: Alice
authors.initials: A
authors.lastname: Pavlowsky
authors.forename: Henriette
authors.initials: H
authors.lastname: Skala
authors.forename: Stéphane
authors.initials: S
authors.lastname: Heitz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vitale
authors.forename: Bernard
authors.initials: B
authors.lastname: Poulain
authors.forename: Malik
authors.initials: M
authors.lastname: Khelfaoui
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Pierre
authors.initials: P
authors.lastname: Billuart
authors.forename: Yann
authors.initials: Y
authors.lastname: Humeau
mesh_terms: D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D064026:Calbindins; D002531:Cerebellum / Q000166:cytology* / Q000254:growth & development*; D004558:Electric Stimulation / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000235:genetics; D066298:In Vitro Techniques; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D000072179:Interleukin-1 Receptor-Like 1 Protein; D051379:Mice; D018345:Mice, Knockout; D009433:Neural Inhibition / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D051580:Neuronal Calcium-Sensor Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D010320:Parvalbumins / Q000378:metabolism; D018408:Patch-Clamp Techniques / Q000379:methods; D011810:Quinoxalines / Q000494:pharmacology; D018123:Receptors, Interleukin / Q000172:deficiency / Q000502:physiology*; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D000779:Anesthetics, Local; D064026:Calbindins; D018691:Excitatory Amino Acid Antagonists; C486189:Il1rl1 protein, mouse; D000072179:Interleukin-1 Receptor-Like 1 Protein; D051580:Neuronal Calcium-Sensor Proteins; D009479:Neuropeptides; D010320:Parvalbumins; D011810:Quinoxalines; D018123:Receptors, Interleukin; D064030:S100 Calcium Binding Protein G; C101464:frequenin calcium sensor proteins; C062865:2,3-dioxo-6-nitro-7-sulfamoylbenzo(f)quinoxaline; D013779:Tetrodotoxin