title: Oxygen-glucose deprivation increases firing of unipolar brush cells and enhances spontaneous EPSCs in Purkinje cells in the vestibulo-cerebellum.
abstract: Unipolar brush cells (UBCs) are excitatory interneurons in the granular layer of the cerebellar cortex, which are predominantly distributed in the vestibulo-cerebellar region. The unique firing properties and synaptic connections of UBCs may underlie lobular heterogeneity of excitability in the granular layer and the susceptibility to ischemia-induced excitotoxicity. In this study, we investigated the effects of oxygen-glucose deprivation (OGD) on the firing properties of UBCs and granule cells and spontaneous excitatory postsynaptic currents (sEPSCs) of Purkinje cells using whole-cell recordings. Short-term OGD induced increases in spontaneous firing of UBCs by causing membrane depolarization via the activation of NMDA receptors. UBC firing indirectly affected Purkinje cells by altering parallel fiber inputs of a subset granule cells, resulting in a marked increase in sEPSCs in Purkinje cells in vestibulo-cerebellar lobules IX-X, but not in lobules IV-VI, which have fewer UBCs. Similarly, the frequency and amplitude of sEPSCs in Purkinje cells were significantly greater in lobules IX-X than in IV-VI, even in control conditions. These results reveal that UBCs play key roles in regulating local excitability in the granular layer, resulting in lobular heterogeneity in the susceptibility to ischemic insult in the cerebellum.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. Electronic address: takayasu@gunma-u.ac.jp.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Takayasu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Shino
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Osamu
authors.initials: O
authors.lastname: Nikkuni
authors.affiliation: Gunma University Heavy Ion Medical Center, Maebashi, Gunma 371-8511, Japan.
authors.forename: Yukari
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Furuya
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Chikamatsu
mesh_terms: D000200:Action Potentials; D000818:Animals; D000831:Animals, Newborn; D065814:Cerebellar Vermis / Q000166:cytology / Q000502:physiology; D002531:Cerebellum / Q000166:cytology / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials; D005260:Female; D005947:Glucose / Q000172:deficiency*; D007395:Interneurons / Q000502:physiology*; D008297:Male; D010100:Oxygen / Q000378:metabolism*; D011689:Purkinje Cells / Q000502:physiology*; D017208:Rats, Wistar
chemical_list: D005947:Glucose; D010100:Oxygen
keywords: Cerebellum; Excitotoxicity; Ischemia; NMDA; Oxygen–glucose deprivation; Unipolar brush cells; Vestibulo-cerebellar lobules