Diminished climbing fiber innervation of Purkinje cells in the cerebellum of myosin Va mutant mice and rats
| Autor: | Yoshiharu Murata, Akira Mizoguchi, Yoshiko Takagishi, Masanobu Kano, Tetsuro Kayahara, Kouichi Hashimoto, Hiroyuki Otsuka, Masahiko Watanabe |
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| Rok vydání: | 2007 |
| Předmět: |
Male
Cerebellum cerebellum Myosin Type V Purkinje cell Presynaptic Terminals Biotin Olivary Nucleus Biology Nervous System Malformations Synaptic Transmission Rats Mutant Strains Cerebellar Cortex Mice Purkinje Cells Cellular and Molecular Neuroscience Microscopy Electron Transmission Developmental Neuroscience Ca^2＋ signaling Myosin medicine Animals Calcium Signaling development Actin Afferent Pathways Biotinylated dextran amine Myosin Heavy Chains Excitatory Postsynaptic Potentials Cell Differentiation Dextrans Climbing fiber Mice Mutant Strains Rats Cell biology Protein Transport medicine.anatomical_structure climbing fiber Axoplasmic transport Excitatory postsynaptic potential Female axonal transport myosin Va mutant mouse Neuroscience |
| Zdroj: | Developmental Neurobiology. 67:909-923 |
| ISSN: | 1932-846X 1932-8451 |
| Popis: | Myosin Va is an actin-based molecular motor that is involved in organelle transport and membrane trafficking. Here, we explored the role of myosin Va in the formation of synaptic circuitry by examining climbing fiber (CF) innervation of Purkinje cells (PCs) in the cerebella of dilute-neurological (d-n) mice and dilute-opisthotonus (dop) rats that have mutations in dilute–encoded myosin Va. Anterograde labeling of CFs with biotinylated dextran amine (BDA) revealed that they arborized poorly and that their tips extended only half way through the thickness of the molecular layer (ML) in adult d-n mice. Using immunohistochemistry specific for vesicular glutamate transporter 2 (VGluT2) to visualize CF synaptic terminals, we found that during development and in adulthood, these terminals did not ascend as far along the proximal shaft dendrites of PCs in d-n mice and dop rats as they did in normal animals. An irregular distribution of BDA-labeled bulbous varicosities and VGluT2 spots along CF branches were also noted in these animals. Finally, VGluT2-positive CF terminals were occasionally localized on the PC somata of adult d-n cerebella. These phenotypes are consistent with our electrophysiological findings that CF-mediated excitatory postsynaptic currents (EPSCs) were significantly smaller in amplitude and faster in decay in adult d-n mice, and that the regression of multiple CFs was slightly delayed in developing d-n mice. Taken together, our results suggest that myosin Va is essential for terminal CF extension and for the establishment of CF synapses within the proper dendritic territories of PCs. Running title: Climbing fibers in myosin Va mutants |
| Databáze: | OpenAIRE |
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