Cav2.1 in Cerebellar Purkinje Cells Regulates Competitive Excitatory Synaptic Wiring, Cell Survival, and Cerebellar Biochemical Compartmentalization
| Autor: | Manabu Abe, Hiroshi Usui, Miwako Yamasaki, Maya Yamazaki, Kenji Sakimura, Taisuke Miyazaki, Masanobu Kano, Kouichi Hashimoto, Masahiko Watanabe |
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| Rok vydání: | 2012 |
| Předmět: |
Cerebellum
Cell Survival Purkinje cell Cav2.1 Mice Purkinje Cells Calcium Channels N-Type Organ Culture Techniques Postsynaptic potential medicine Animals Mice Knockout biology Voltage-dependent calcium channel Aldolase C General Neuroscience Excitatory Postsynaptic Potentials Articles Climbing fiber Cell Compartmentation Mice Inbred C57BL medicine.anatomical_structure Animals Newborn Synapses biology.protein Excitatory postsynaptic potential Neuroscience |
| Zdroj: | The Journal of Neuroscience. 32:1311-1328 |
| ISSN: | 1529-2401 0270-6474 |
| DOI: | 10.1523/jneurosci.2755-11.2012 |
| Popis: | In the adult cerebellum, each Purkinje cell (PC) is innervated by a single climbing fiber (CF) in proximal dendrites and 105-106parallel 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. |
| Databáze: | OpenAIRE |
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