title: Type 1 inositol trisphosphate receptor regulates cerebellar circuits by maintaining the spine morphology of purkinje cells in adult mice.
abstract: The structural maintenance of neural circuits is critical for higher brain functions in adulthood. Although several molecules have been identified as regulators for spine maintenance in hippocampal and cortical neurons, it is poorly understood how Purkinje cell (PC) spines are maintained in the mature cerebellum. Here we show that the calcium channel type 1 inositol trisphosphate receptor (IP3R1) in PCs plays a crucial role in controlling the maintenance of parallel fiber (PF)-PC synaptic circuits in the mature cerebellum in vivo. Significantly, adult mice lacking IP3R1 specifically in PCs (L7-Cre;Itpr1(flox/flox)) showed dramatic increase in spine density and spine length of PCs, despite having normal spines during development. In addition, the abnormally rearranged PF-PC synaptic circuits in mature cerebellum caused unexpectedly severe ataxia in adult L7-Cre;Itpr1(flox/flox) mice. Our findings reveal a specific role for IP3R1 in PCs not only as an intracellular mediator of cerebellar synaptic plasticity induction, but also as a critical regulator of PF-PC synaptic circuit maintenance in the mature cerebellum in vivo; this mechanism may underlie motor coordination and learning in adults.
authors.affiliation: Laboratories for Developmental Neurobiology, RIKEN Brain Science Institute, Wako, Saitama 351-0198, Japan.
authors.forename: Takeyuki
authors.initials: T
authors.lastname: Sugawara
authors.forename: Chihiro
authors.initials: C
authors.lastname: Hisatsune
authors.forename: Tung Dinh
authors.initials: TD
authors.lastname: Le
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Hashikawa
authors.forename: Moritoshi
authors.initials: M
authors.lastname: Hirono
authors.forename: Mitsuharu
authors.initials: M
authors.lastname: Hattori
authors.forename: Soichi
authors.initials: S
authors.lastname: Nagao
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
mesh_terms: D000818:Animals; D002524:Cerebellar Ataxia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D002531:Cerebellum / Q000166:cytology / Q000473:pathology / Q000502:physiology*; D002678:Chimera; D049229:Dendritic Spines / Q000473:pathology / Q000502:physiology*; D005260:Female; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009473:Neuronal Plasticity / Q000502:physiology; D017120:Nystagmus, Optokinetic / Q000502:physiology; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology* / Q000648:ultrastructure; D012027:Reflex, Vestibulo-Ocular / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D053496:Inositol 1,4,5-Trisphosphate Receptors; C025389:Itpr1 protein, mouse