title: Carbonic anhydrase related protein 8 mutation results in aberrant synaptic morphology and excitatory synaptic function in the cerebellum.
abstract: Carbonic anhydrase related protein 8 (Car8) is known to be abundantly expressed in Purkinje cells (PCs), and its genetic mutation causes a motor coordination defect. To determine the underlying mechanism, we analyzed the mouse cerebellum carrying a Car8 mutation. Electrophysiological analysis showed that spontaneous excitatory transmission was largely diminished while paired pulse ratio at parallel fiber-PC synapses was comparable to wild-type, suggesting functional synapses have normal release probability but the number of functional synapses may be lower in mutants. Light microscopic study revealed an abnormal extension of climbing fibers to the distal PC dendrites. At the ultrastructural level, we found numerous PC spines not forming synapses primarily in distal dendrites and occasionally multiple spines contacting a single varicosity. These abnormalities of parallel fiber-PC synapses may underlie the functional defect in excitatory transmission. Thus, Car8 plays a critical role in synaptogenesis and/or maintenance of proper synaptic morphology and function in the cerebellum.
authors: Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B 3V6. michiru@mun.ca
authors: Michiru
authors: M
authors: Hirasawa
authors: Xinjie
authors: X
authors: Xu
authors: Robert B
authors: RB
authors: Trask
authors: Terry P
authors: TP
authors: Maddatu
authors: Britt A
authors: BA
authors: Johnson
authors: Jürgen K
authors: JK
authors: Naggert
authors: Patsy M
authors: PM
authors: Nishina
authors: Akihiro
authors: A
authors: Ikeda
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000502:physiology; D002526:Cerebellar Diseases / Q000235:genetics / Q000473:pathology* / Q000503:physiopathology*; D002531:Cerebellum / Q000473:pathology / Q000502:physiology; D049229:Dendritic Spines / Q000201:enzymology / Q000473:pathology / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008818:Mice, Neurologic Mutants; D008854:Microscopy, Electron; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology; D011689:Purkinje Cells / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D013569:Synapses / Q000473:pathology* / Q000502:physiology / Q000648:ultrastructure; D002256:Carbonic Anhydrases
chemical_list: D014408:Biomarkers, Tumor; D009419:Nerve Tissue Proteins; C512821:Car8 protein, mouse; D002256:Carbonic Anhydrases