title: Cav2.1 in cerebellar Purkinje cells regulates competitive excitatory synaptic wiring, cell survival, and cerebellar biochemical compartmentalization.
abstract: In the adult cerebellum, each Purkinje cell (PC) is innervated by a single climbing fiber (CF) in proximal dendrites and 10(5)-10(6) parallel fibers (PFs) in distal dendrites. This organized wiring is established postnatally through heterosynaptic competition between PFs and CFs and homosynaptic competition among multiple CFs. Using PC-specific Cav2.1 knock-out mice (PC-Cav2.1 KO mice), we have demonstrated recently that postsynaptic Cav2.1 plays a key role in the homosynaptic competition by promoting functional strengthening and dendritic translocation of single "winner" CFs. Here, we report that Cav2.1 in PCs, but not in granule cells, is also essential for the heterosynaptic competition. In PC-Cav2.1 KO mice, the extent of CF territory was limited to the soma and basal dendrites, whereas PF territory was expanded reciprocally. Consequently, the proximal somatodendritic domain of PCs displayed hyperspiny transformation and fell into chaotic innervation by multiple CFs and numerous PFs. PC-Cav2.1 KO mice also displayed patterned degeneration of PCs, which occurred preferentially in aldolase C/zebrin II-negative cerebellar compartments. Furthermore, the mutually complementary expression of phospholipase Cβ3 (PLCβ3) and PLCβ4 was altered such that their normally sharp boundary was blurred in the PCs of PC-Cav2.1 KO mice. This blurring was caused by an impaired posttranscriptional downregulation of PLCβ3 in PLCβ4-dominant PCs during the early postnatal period. A similar alteration was noted in the banded expression of the glutamate transporter EAAT4 in PC-Cav2.1 KO mice. Therefore, Cav2.1 in PCs is essential for competitive synaptic wiring, cell survival, and the establishment of precise boundaries and reciprocity of biochemical compartments in PCs.
authors.affiliation: Department of Anatomy, Hokkaido University School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Miwako
authors.initials: M
authors.lastname: Yamasaki
authors.forename: Kouichi
authors.initials: K
authors.lastname: Hashimoto
authors.forename: Maya
authors.initials: M
authors.lastname: Yamazaki
authors.forename: Manabu
authors.initials: M
authors.lastname: Abe
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Usui
authors.forename: Masanobu
authors.initials: M
authors.lastname: Kano
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D020864:Calcium Channels, N-Type / Q000502:physiology*; D002451:Cell Compartmentation / Q000502:physiology*; D002470:Cell Survival / Q000502:physiology; D002531:Cerebellum / Q000737:chemistry / Q000166:cytology / Q000502:physiology; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D011689:Purkinje Cells / Q000737:chemistry / Q000502:physiology*; D013569:Synapses / Q000737:chemistry / Q000502:physiology*
chemical_list: D020864:Calcium Channels, N-Type