若手道場

若手道場情動の分子基盤

7月7日（金）　9:30-10:15　Room D 2W②-1 成長期のエストラジオール低下による社会的行動への影響 Effects of decreased estradiol during growth on social behavior 古川　恵^1,2, 青木　亮憲², 東方　優大³, 眞部　孝幸⁴, 出雲　信夫^3,5, 松崎　秀夫^1,6 1. 大阪大学大学院　連合小児発達学研究科　脳機能発達学, 2. 横浜薬科大学　薬学教育センター, 3. 横浜薬科大学　薬物治療学研究室, 4. 中京学院大学　看護学部看護学科, 5. 横浜薬科大学　総合健康メディカル研究センター, 6. 福井大学　子どものこころの発達研究センター　脳機能発達研究部門 Megumi Furukawa^1,2, Ryoken Aoki², Masahiro Toho³, Takayuki Manabe⁴, Nobuo Izumo^3,5, Hideo Matsuzaki^1,6 1. Div. of Dev. Higher Brain Funct. (Univ. of Fukui), United Graduate School of Child Dev., Osaka Univ., Fukui, Japan, 2. Ctr. for pharm. Educ., Yokohama Univ. of Pharmacy, Yokohama, Japan, 3. Lab. of Pharmacotherapy, Yokohama Univ. of Pharmacy, Yokohama, Japan, 4. Lab. for Neuroanatomy and Neuropharmacology, Dept. of Nursing, Faculty of Nursing, Chukyogakuin Univ., Gifu, Japan, 5. Gen. Health Med. Res. Ctr., Yokohama Univ. of Pharmacy, Yokohama, Japan, 6. Res. Ctr. for Child Mental Dev., Univ. of Fukui, Fukui, Japan Estradiol is believed to play an important role in social behavior by regulating neurotransmitter. Besides, it has been suggested that estradiol is involved social behavioral deficits of psychiatric disorders such as autism spectrum disorder, anxiety disorders and major depressive disorder. However, its role in social functioning in childhood is still poorly understood. In this study, we investigated the effect of decreased estradiol in childhood on social behavior in adolescence using the ovariectomized mice model.The female ICR mice of 4-weeks of age were received ovariectomy or sham operation. At 10-weeks of age, to assess social interaction, we performed three-chamber social behavior test. Moreover, release amount of serotonin in amygdala were measured using microdialysis.We showed that time spent of novel mouse was higher than contacted mouse in OVX group, although no differences were observed between time spent of novel and contacted mouse in sham group. As the result of microdialysis, compared with sham group, release amount of serotonin was significantly higher than that of OVX group.Our data indicated that decreased estradiol in childhood effects differences in preference between a novel and a familiar animal. Furthermore, we speculate estradiol modulates social behavior via the serotonergic nervous system.		7月7日（金）　9:30-10:15　Room D 2W②-2 Exposure of conditioned stimuli in multiple contexts enhances fear extinction memories 福永　祐一, Shania Gonzalez, Emily Lock, Schulman Emma, Victor Cazares ウィリアムズ大学 Yuichi Fukunaga, Shania Gonzalez, Emily Lock, Schulman Emma, Victor Cazares Psychology Department and Neuroscience Program, Williams College, Williamstown, MA, USA Fear extinction is context-specific; thus if an extinguished conditioned stimulus (CS) is experienced in any context except for the one in which it was extinguished, the CS will re-elicit the fear response, a phenomenon termed fear renewal. We previously showed that fear extinction training in multiple novel contexts overcomes fear renewal, enhances extinction learning, and improves extinction recall 7 days later. The present study extends these findings to report that multiple context fear extinction (MCFE) suppresses spontaneous recovery (when tested 30 days after extinction). We also report that contextual novelty in MCFE is not necessary since exposure to multiple familiar contexts still enhances fear extinction memories. Furthermore, we show that enhancement of fear extinction in the MCFE paradigm requires the hippocampus since chemogenetic activation or inhibition of hippocampal cells impairs extinction recall when animals were trained in multiple contexts, but not in a single context. Finally, to ascertain how fear engrams evolve during extinction training, we labeled Fos-expressing neurons using TRAP (Targeted Recombination in Active Populations) and immunohistochemistry. Altogether, our results suggest that hippocampal cell activation is necessary for generalization and consolidation of contextually distinct extinction memories.

7月7日（金）　9:30-10:15　Room D 2W②-3 Na+/Ca2+ 交換輸送体3（NCX3）ヘテロ型欠損マウスにおける認知機能障害及び多動性行動に関する研究 Hyperactivity and memory deficits induced by dopaminergic dysfunction in NCX3 heterozygous mice 稲垣　良¹, 喜多　紗斗美², 丹羽　望¹, 岩本　隆宏³, 森口　茂樹¹ 1. 東北大学　薬　医薬品開発研究センター, 2. 徳島文理大学　薬　薬理, 3. 福岡大学　医　薬理 Ryo Inagaki¹, Satomi Kita², Nozomu Niwa¹, Takahiro Iwamoto³, Shigeki Moriguchi¹ 1. Research Center for Pharmaceutical Development, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan, 2. Department of Pharmacology, Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Tokushima, Japan, 3. Department of pharmacology, Faculty of Medicine, Fukuoka University, Fukuoka, Japan Na+/ Ca2+ exchangers (NCXs) are predominantly expressed in the plasma membrane and consist of three mammalian NCX isoforms (NCX1, NCX2, and NCX3). Here, we report that NCX3 heterozygous (NCX3+/-) mice exhibited hyperactivity and memory impairment, which are ameliorated by the treatment of methylphenidate. NCX3+/- mice displayed impairment of LTP induction in the prefrontal cortex (PFC) and hippocampus, a phenotype that of NCX3+/- mice was correlated with persistent activation of CaMKII and memory impairment. However, treatment of methylphenidate rescued the induction of LTP and CaMKII persistent activation only in the PFC but not in the hippocampus of NCX3+/- mice. We also observed increase of extracellular dopamine levels in the PFC of NCX3+/- mice by in vivo microdialysis measurement. In concordance with the increase of extracellular dopamine levels in the PFC, NCX3+/- mice exhibited the activation of dopamine D1 receptor signaling pathways including DARPP-32 and GluA1 relative to WT mice in the PFC. Thus, the decreased expression of NCX3 leads to impair dopaminergic neurotransmission in the PFC, which likely accounts for the hyperactivity and memory deficits in NCX3+/- mice.