一般ポスター

一般ポスターシナプス形成

7月6日（木）　13:20-14:20　ポスター会場① 1P②-1 シナプス後肥厚部(PSD)構造と重合中微小管の相互作用の解析 Interaction between postsynaptic density (PSD) and polymerizing tubulin 鈴木　龍雄¹, 藤井　敏弘², 亀谷　清和³, 田渕　克彦⁴ 1. 信州大学医学部, 2. 信州大学繊維学部, 3. 酪農学園大学獣医学部獣医解剖学教室, 4. 信州大学学術研究院バイオメディカル研究所 Tatsuo Suzuki¹, Toshihiro Fujii², Kiyokazu Kametani³, Katsuhiko Tabuchi⁴ 1. Dept. Molecular & Cellular Physiology, Shinshu Univ, Sch. Med., 2. Shinshu Univ. Textile Sci. & Tech., 3. Dept. Veterinary Anatomy, Veterinary Medicine, Rakuno Gakuen Univ., 4. Shinshu Univ. Inst. Biomedical Sci. A complete understanding of the structure of postsynaptic density (PSD) is essential to fully elucidate the molecular mechanisms of PSD construction and its reorganization. In a previous paper, we purified and examined the PSD lattice structure, which is an essential skeletal structure for PSD and in which non-microtubule tubulin is a major component (Suzuki et al., 2018, 2021) Thus, our previous studies suggest a fundamental role for tubulin in the structure of the PSD at excitatory synapses. Other research groups have shown periodic and transient invasion of microtubules from dendrites to spines (2008), suggesting a role for microtubules in the regulation of spine morphology and the development of synaptic plasticity. Against these backgrounds, we investigated the interaction of PSD and PSD lattice with polymerized tubulin at the electron microscopy level. The PSD lattices were in contact with both ends of microtubules. A meshwork structure similar to the PSD lattice was detected in the purified tubulin preparation, which interacted with the microtubules during polymerization in the same manner. Thus, the PSD lattice structure may share some properties with similar structures found in purified tubulin preparations. This study suggests that the PSD lattice may trap transiently invading microtubules.		7月6日（木）　13:20-14:20　ポスター会場① 1P②-2 Phldb2は海馬の樹状突起スパインの形態を制御する Phldb2 regulates hippocampal dendritic spine morphology 謝　敏かく^1,2,3,4, 佐藤　真^2,4,5 1. 福井大・子どものこころの発達研究センター, 2. 福井大・医・脳形態機能学領域, 3. 福井大・生命科学複合研究教育センター, 4. 大阪大学・金沢大学・浜松医科大学・千葉大学・福井大学連合小児発達学研究科, 5. 大阪大学大学院・医・解剖学講座 Min-Jue Xie^1,2,3,4, Makoto Sato^2,4,5 1. Div brain struc func, Dept Morphol Physiol Sci, Univ of Fukui, Fukui, Japan, 2. Div brain struc func, Dept Morphol Physiol Sci, Univ of Fukui, Fukui, Japan, 3. Res Edu Program Life Sci, Univ of Fukui, 4. United Grad Sch Child Dev, Osaka Univ-Kanazawa Univ-Hamamatsu College Med-Chiba Univ & Univ Fukui, 5. Dept Anat Neurosci, Osaka Univ Grad Sch Med, Osaka, Japan Morphologically dynamic dendritic spines are major sites of neuronal plasticity in the brain, but the molecular mechanisms underlying their morphological dynamics have not been fully elucidated. Phldb2 is a protein that contains two predicted coiled-coil domains and a pleckstrin homology domain whose binding is highly sensitive to PIP3. We previously demonstrated that Phldb2 regulates synaptic plasticity, glutamate receptor trafficking and PSD-95 turnover. Drebrin, such as drebrin A (adult form) and drebrin E (embryonic form), is one of the most abundant neuron-specific F-actin binding protein that is pivotal for synaptic morphology and thereby neurotransmission. We observed here that Phldb2 bound to drebrin A, but not to drebrin E. In the absence of Phldb2, subcellular localization of drebrin A in the hippocampal spines and its whole distribution in the hippocampus were altered. Immature type of spines, such as filopodium type, increased relatively in CA1 regions of the hippocampus, whereas mushroom type of spines, a typical mature type, decreased in Phldb2-/- mice. Phldb2 suppressed the formation of abnormal filopodium structure, which had been induced by drebrin A-overexpression. Taken together, these findings demonstrate that Phldb2 is pivotal for dendritic spine morphology and possibly for neurotransmission in the matured animal through regulating drebrin A localization.

7月6日（木）　13:20-14:20　ポスター会場① 1P②-3 前頭前皮質におけるKirrel3発現細胞の免疫組織学的解析 Immunofluorescence characterization of Kirrel3-exrressing cells in the prefrontal cortex 久岡　朋子, 小森　忠祐, 森川　吉博和歌山県立医科大学 Tomoko Hisaoka, Tadasuke Komori, Yoshihiro Morikawa Wakayama Medical University Mutations of KIRREL3 gene, a synaptic cell-adhesion molecule, have been implicated in autism spectrum disorder (ASD). We have reported that Kirrel3-deficient (Kirrel3^-/-) mice exhibited ASD-like behaviors with hyperactivity. It has been reported that prefrontal cortex (PFC) dysfunction is identified in individuals with ASD. To get insights into the roles of Kirrel3 in the PFC, we characterized Kirrel3-expressing cells in the PFC using Kirrel3-heterozygous mice, in which Kirrel3-expressing cells could be identified by the expression of β-galactosidase (β-gal). β-gal was mostly expressed in GluR2/3⁺ projection neurons. To further identify Kirrel3-expressing neurons, we performed double-immunofluorescence staining for β-gal with Satb2, Ctip2, and DARPP-32, markers of corticocortical, subcortical, and corticothalamic projection neurons, respectively. β-gal was colocalized with Ctip2, but not with DARPP-32. In addition, β-gal was also detected in Satb2⁺ neurons of prelimbic area. Therefore, it is likely that Kirrel3 is expressed in both subcortical and corticocortical projection neurons, but not in corticothalamic projection neurons in the PFC. These results suggest that Kirrel3 may be involved in the formation and maintenance of these circuits. This work was supported by JSPS KAKENHI Grant Numbers JP22390036 and JP21K07525.		7月6日（木）　13:20-14:20　ポスター会場① 1P②-4 成体脳海馬神経新生における酸感受性イオンチャネルASIC1aの役割 Roles of acid-sensing ion channel-1a (ASIC1a) in hippocampal adult neurogenesis 熊本　奈都子, 柴田　泰宏, 植田　高史, 鵜川　眞也名市大　院医　機能組織学 Natsuko Kumamoto, Yasuhiro Shibata, Takashi Ueda, Shinya Ugawa Dept. of Anat. and Neurosci., Nagoya City Univ., Grad. Sch. of Med. Sci., Aichi, Japan Adult neural stem cells (NSCs) in the subgranular zone (SGZ) of the hippocampal dentate gyrus continuously generate new neurons throughout life and they are integrated into existing neural circuits via synaptogenesis. NSCs live in a relatively hypoxic microenvironment and hypoxia can stimulate the proliferation and differentiation of NSCs, raising the sufficient possibility that protons in the SGZ are involved in the regulation of neurogenesis. We then focused on the acid-sensing ion channel-1a (ASIC1a), a neuronal proton-activated cation channel, and investigated the role of ASIC1a in hippocampal neurogenesis in the adult mouse brain. We found that ASIC1a is expressed in progenitor cells from the early stage of hippocampal neurogenesis and that cell proliferation is enhanced in ASIC1a knockout (KO) mice. These data suggest that ASIC1a is involved with the proliferation of progenitor cells. The effects of ASIC1a on dendritic development and synaptogenesis in the newborn neurons were also investigated since ASIC1a expression is particularly strong at the time when dendrites of immature neurons develop and when new synapses form between new and mature neurons of the hippocampal circuits. Our results indicate that ASIC1a is also required for dendritic development and synaptic organization of mouse hippocampal newborn neurons.

7月6日（木）　13:20-14:20　ポスター会場① 1P②-5 NMDAによるCaMKII-RhoA-Rho-kinase経路の活性化が忌避学習を制御する NMDA-induced activation of the CaMKII-RhoA-Rho-kinase pathway regulates aversive learning 船橋　靖広^1,2, Rijwan Uddin Ahammad^1,2, 張　心健³, Hossen Emran^1,2, Md. Omar Faruk^1,2, 呉　敏華^1,2, 王　緩緩^1,2, 李　旭^1,2, 黒田　啓介⁴, 坪井　大輔^1,2, 西岡　朋生^1,2, 天野　睦紀⁴, 崎村　建司⁶, 内野　茂夫⁷, 山田　清文⁵, 永井　拓³, 貝淵　弘三^1,2 1. 藤田医科大学医科学研究センター, 2. 藤田医科大学精神・神経病態解明センター細胞生物部門, 3. 藤田医科大学精神・神経病態解明センター神経行動薬理学研究部門, 4. 名古屋大学大学院医学系研究科神経情報薬理学, 5. 名古屋大学大学院医学系研究科医療薬学, 6. 新潟大学脳研究所モデル動物開発分野, 7. 帝京大学理工学部バイオサイエンス学科 Yasuhiro Funahashi^1,2, Rijwan Uddin Ahammad^1,2, Xinjian Zhang³, Hossen Emran^1,2, Md. Omar Faruk^1,2, Minhua Wu^1,2, Huanhuan Wang^1,2, Xu Li^1,2, Keisuke Kuroda⁴, Daisuke Tsuboi^1,2, Tomoki Nishioka^1,2, Mutsuki Amano⁴, Kenji Sakimura⁶, Shigeo Uchino⁷, Kiyofumi Yamada⁵, Taku Nagai³, Kozo Kaibuchi^1,2 1. Center for Medical Science, Fujita Health University, Aichi, Japan, 2. Division of cell biology, International Center for Brain Science (ICBS), Fujita Health University, Toyoake, Aichi, Japan, 3. Division of Behavioral Neuropharmacology, International Center for Brain Science (ICBS), Fujita Health University, Aichi, Japan, 4. Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Aichi, Japan, 5. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Aichi, Japan, 6. Department of Animal Model Development, Brain Research Institute, Niigata University, Niigata, Japan, 7. Department of Biosciences, School of Science and Engineering, Teikyo University, Tochigi, Japan Glutamate induces neuronal Ca²⁺ influx by binding to N-methyl-D-aspartate (NMDA) receptors, thereby activating Ca²⁺-dependent protein kinases, including CaMKII, which play critical roles in synaptic plasticity and learning. However, the mechanisms by which these kinases regulate synaptic plasticity and learning remain largely unknown. We performed phosphoproteomic analyses to explore phosphorylation signals downstream of NMDA receptors in mouse striatal/accumbal slices. We identified 159 proteins, including Rho GTPase regulators, whose phosphorylation was promoted by NMDA. CaMKII phosphorylated ARHGEF2 and stimulated its RhoGEF activity. Aversive stimuli induced CaMKII-mediated ARHGEF2 phosphorylation and Rho-kinase/ROCK activation in the nucleus accumbens (NAc). Rho-kinase inhibition in the NAc attenuates aversive learning. We screened Rho-kinase substrates and identified 221 proteins, including SHANK3. Rho-kinase-mediated phosphorylation of SHANK3 increased its interaction with DLGAP3. SHANK3 manipulation in the NAc regulated dendritic spine formation and aversive learning in a phosphorylation-dependent manner. Thus, NMDA activation of the CaMKII-ARHGEF2-Rho-kinase pathway induces SHANK3 phosphorylation for aversive learning.