title: Plasticity of the developmentally arrested staggerer cerebellum in response to exogenous RORα.
abstract: Retinoid-related orphan receptor α (RORα) is a critical master transcription factor that governs postnatal cerebellar development. An RORα-deficient cerebellum has a persistent external granular layer (EGL), rudimentary Purkinje cell (PC) dendrites, grossly reduced numbers of immature parallel fiber (PF)-PC synapses, and multiple climbing fibers (CF) innervating PCs in mice after 3 weeks of age when these features have disappeared in wild-type mice. Functionally, metabotropic glutamate receptor (mGluR)-mediated signaling in PCs is completely abrogated. Here we examined whether these defects could be corrected by lentivirally providing the RORα gene to 3-week-old PCs of RORα-deficient homozygous staggerer (sg/sg) mice. RORα expression in sg/sg PCs significantly increased the numbers of PF-PC synapses, spines on PC dendritic branchlets, and internal granule cells, concomitant with regression of the EGL, suggesting enhanced proliferation in the EGL and migration of post-mitotic progeny into the internal granular layer with augmented synaptogenesis between PFs and PC dendrites. However, the primary dendritic stems were only slightly extended, and mGluR signaling and the loss of redundant CF synapses in sg/sg PCs remained unrestored. These results suggest that the mitogenic and migratory potential of external granule cells in response to RORα was preserved in the >3-week-old sg/sg mouse cerebellum. Moreover, sg/sg PCs sprouted spines and formed synapses with PFs. However, lengthening of the primary dendritic stems, establishment of mGluR signaling, and removal of CF synapses in sg/sg PCs were regressed by 3 weeks of age.
authors.affiliation: Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Iizuka
authors.affiliation: Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Matsuzaki
authors.affiliation: Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan.
authors.forename: Ayumu
authors.initials: A
authors.lastname: Konno
authors.affiliation: Department of Neurophysiology, Gunma University Graduate School of Medicine, Maebashi, Gunma, 371-8511, Japan. hirai@gunma-u.ac.jp.
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Hirai
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000166:cytology / Q000254:growth & development*; D003712:Dendrites / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials; D005822:Genetic Vectors; D006801:Humans; D016086:Lentivirus / Q000502:physiology; D008564:Membrane Potentials; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D009473:Neuronal Plasticity; D057094:Nuclear Receptor Subfamily 1, Group F, Member 1 / Q000235:genetics / Q000502:physiology*; D011689:Purkinje Cells / Q000166:cytology / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000502:physiology; D013569:Synapses / Q000502:physiology
chemical_list: D057094:Nuclear Receptor Subfamily 1, Group F, Member 1; C539738:RORA protein, human; D018094:Receptors, Metabotropic Glutamate
keywords: Cerebellum; Lentiviral vector; Plasticity; Purkinje cell; RORα; Staggerer mouse