若手道場
シナプス形成 |
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| 7月6日（木） 9:00-10:00 Room H
1W①-1
大脳皮質ニューロンにおけるシナプス活性化はSRF転写コアクチベーターMRTFAをリン酸化し、転写を制御する
Neuronal activity induces phosphorylation of the SRF coactivator MRTFA and SRF-dependent transcription in neurons
中島 朋美1, 伊原 大輔2, 櫻井 宏明3, 田渕 明子2
1. 富山大学 大学院医薬理工学環認知・情動脳科学プログラム 分子神経生物学, 2. 富山大学 学術研究部薬学・和漢系 分子神経生物学, 3. 富山大学 学術研究部薬学・和漢系 がん細胞生物学
Tomomi Nakajima1, Daisuke Ihara2, Hiroaki Sakurai3, Akiko Tabuchi2
1. Lab. Mol. Neurobiol.,Glad.Sch. Pharm-Med. Sci.,Glad. Prog.Cognitive and Emotional Neurosci., Univ. of TOYAMA, Toyama, Japan, 2. Lab. Mol.Neurobiol., Fac. Pharm. Sci., Univ. of TOYAMA, Toyama, Japan, 3. Lab. Cancer Cell Biol., Fac. Pharm. Sci., Univ. of TOYAMA, Toyama, Japan
Neural plasticity, which is a molecular basis of learning and memory, is associated with gene expression and morphological changes. Currently, we focus on the myocardin-related transcription factor (MRTF) family members which comprise MRTFA and MRTFB. The MRTFs are G-actin bound RPEL proteins which bind to and activate serum response factor (SRF) and regulate gene expression and morphological changes in the brain. Accumulating evidence suggest that protein modifications of MRTF contribute to regulation of their localization and function in non-neuronal cells. However, whether synaptic activity promotes the phosphorylation of MRTF and regulates the function of MRTF in neurons have not yet been fully clarified. In this study, therefore, we are trying to identify the signaling pathways involves in synaptic activity-mediated MRTFA phosphorylation in cortical neurons. We found that MRTFA was transiently phosphorylated by synaptic activity. In addition, this phosphorylation was blocked by inhibition of voltage-gated calcium channel (VGCC) and ERK1/2 pathway, but not by inhibition of CaMK pathway and actin polymerization.Ongoing studies are aimed at identifying the phosphorylation sites of MRTFA involved in the induction of SRF-mediated transcription by constructing an MRTFA mutant and investigating the physiological significance of their phosphorylation. | | 7月6日（木） 9:00-10:00 Room H
1W①-2
TREM2を介してシナプス精緻化および機能的な神経回路を形成する因子の探索
Exploration of TREM2-mediated molecules which regulate functional neural connectivity
池之上 篤志1, 依藤 依代2, 平賀 慎一郎2,3, 糸数 隆秀2,3, 山下 俊英1,2,3,4
1. 大阪大学大学院 生命機能研究科 分子神経科学, 2. 大阪大学大学院 医学系研究科 分子神経科学, 3. 大阪大学大学院 医学系研究科 創薬神経科学, 4. 免疫フロンティア研究センター
Atsushi Ikenoue1, Iyo Yorifuji2, Sin-ichiro Hiraga2,3, Takahide Itokazu2,3, Toshihide Yamashita1,2,3,4
1. Department of Molecular Neuroscience, Graduate School of Frontier Biosciences, Osaka University, 2. Department of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 3. Department of Neuro-Medical Science, Graduate School of Medicine, Osaka University, 4. WPI Immunology Frontier Research Center
In the developing brain, the construction of functional neural circuit is a dynamic process consisting of both synaptic formation and elimination. Around birth, exuberant synaptic connections are formed, and then unnecessary synapses are eliminated by microglia, brain-resident immune cells . Recent study suggests that lack of triggering receptor expressed on myeloid cells 2 (TREM2) impairs synapse elimination, which is accompanied by the reduced neural connectivity and Autistic-like behavior. Although it is known that TREM2 is mainly expressed by microglia, how TREM2-mediated molecules regulate neural connectivity has yet to be fully elucidated. We first examined the expression of Trem2 by qRT-PCR using FACS-sorted hippocampal microglia. Trem2 showed higher expression in microglia obtained at the active stage of synaptogenesis (3 weeks), compared to the following phase of neural circuit maturation (8 weeks). In Trem2 KO mice, the expression of a synaptic marker (PSD95) in the hippocampus was increased compared to WT mice, suggesting the impairment of synapse elimination by Trem2 KO. Therefore, to identify the factors regulating functional neural connectivity, we performed RNA-seq using WT and Trem2 KO hippocampus at the timing of synapse maturation (4 weeks). Based on the results, functional analysis of candidate genes which regulate neural connection is in progress. | | 7月6日（木） 9:00-10:00 Room H
1W①-3
精神疾患モデルマウスにおける前頭前野局所回路へのニューロモデュレーションの効果
Effects of neuromodulation on local prefrontal circuits in mouse models for psychiatric disorders.
池原 実伸1, 山室 和彦1, 法山 勇樹1, 齋藤 康彦2, 牧之段 学1
1. 奈良県立医科大学 精神医学講座, 2. 奈良県立医科大学第一生理学講座
Minobu Ikehara1, Kazuhiko Yamamuro1, Yuki Noriyama1, Yasuhiko Saito2, Manabu Makinodan1
1. Department of Psychiatry, Nara Medical University
Recently, noninvasive neuromodulation by rTMS has been attracting attention as a treatment for psychiatric disorders, and it has been indicated for depression in Japan. In this study, we used deep brain stimulation (DBS), a neuromodulation technique, to locally stimulate the medial prefrontal cortex (mPFC) in mice because rTMS affects the entire brain.
We used DBS (20 min/day for 6 days) to test social behavior (3-chamber task), fear memory (fear conditioning), depressive symptoms (tail suspension test), and activity- and anxiety-related behaviors (open field and elevated plus maze) in a restraint stress model（RS）, a social defeat model（SD）, and juvenile isolation model mice(jSI). RS and SD commonly showed depressive symptoms, which were improved by DBS. Social behavior was decreased in jSI and SD, but improved with DBS.
Next, we examined the effects of DBS on local neural circuits in mPFC using the whole-cell patch clamp technique. sIPSC input frequency to LayerV/VI pyramidal cells was significantly increased by DBS stimulation (20 min/day for 6 days). An increase in sEPSC frequency and a decrease in sIPSC frequency were also observed in LayerV/VI PV interneurons. These results suggest that DBS may affect PFC local circuits and ameliorate behavioral abnormalities in each mouse model. | | 7月6日（木） 9:00-10:00 Room H
1W①-4
Role of microglia in dendritic spine changes of dentate gyrus granule cells after cerebral ischemia.
岡田 桃花, 中澤 秀真, 山口 菜摘, 中谷 仁, 澤野 俊憲, 田中 秀和
立命館大学 生命科学部 生命医科学科 薬理学研究室
Momoka Okada, Shuma Nakazawa, Natsumi Yamaguchi, Jin Nakatani, Toshinori Sawano, Hidekazu Tanaka
Pharmacology Laboratory, Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University
Microglia contribute to the synaptic pruning by synaptic engulfment, which is dependent on neuronal activity. We previously demonstrated that neuronal activation is drastically upregulated in the hippocampal dentate gyrus (DG) after cerebral ischemia, even though an ischemic area does not cover the hippocampal area in our middle cerebral artery occlusion (MCAO) mice. In this study, we investigated dendritic spine changes in DG granule cells after cerebral ischemia and microglial contribution to it. We found that dendritic spine density of DG granule cells in MCAO mice was lower than that in sham mice. However, microglial depletion with CSF1R inhibitor (PLX3397) inhibited the MCAO-induced reduction of spine density. These results suggest that microglia are involved in the decrease in the number of dendritic spines of DG granule cells after cerebral ischemia. | |
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