一般口演（Oral）

Oral Mechanisms for Sociability: Neural circuits for social interactions 一般口演社会性の成立機序：社会的交流を司る神経回路

7月25日（木）14:55～15:10　第9会場（朱鷺メッセ　3F　306+307） 1O-09a1-2 群居本能を制御する神経回路機構 Kansai Fukumitsu（福光甘斎），Misato Kaneko（金子美里），Yukimi Arai（新井幸美），Hazuki Inoue（井上巴月），Kumi Kuroda（黒田公美）理化学研究所脳神経科学研究センター Socially living animals live in groups. This inborn tendency to act in a group is called "herd instinct". Therefore, separation from a group causes emotional distress called "separation distress". Long-term social separation (loneliness) has been thought to be risk factors for mental illnesses including increased depressive symptomatology. Maternal separation in nonhuman primates and guinea pigs is known to be an animal model of "separation distress". Two-stage responses are observed during maternal separation, "separation anxiety" response and "depressive" response, respectively. Based on classical studies with infant guinea pigs, subcortical/limbic regions such as the anterior cingulate area (ACC) and bed nucleus of the stria terminalis (BNST) are thought to be involved in separation anxiety. Social huddle behaviors in rodent are observed during a light period (sleeping together in a huddle) and in a fear situation (defensive huddle). Previous research showed that oxytocin signaling plays a key role in modulating these behaviors. However, the neural basis of herd instinct has remained elusive. Here, we developed a new assay system for "herd instinct" by performing quantitative analysis of separation anxiety and huddle behavior in adult female mice and identified the brain regions potentially involved in these behaviors. We examined c-Fos expression patterns induced by social separation and reunion in the Amygdala-BST-hypothalamic sub nuclei. We found that CaMKIIa-expressing central amygdala neurons, particularly its medial part (CeM) were especially activated by social separation. On the other hand, the anterior part of the hypothalamic area was activated by social reunion. Chemogenetic activation of CaMKIIa neurons in CeM caused an enhancement of separation anxiety. On the other hand, NMDA lesions of the anterior part of the hypothalamic area disrupted huddle behavior. Our findings illustrate how central amygdala and hypothalamic area regulate separation anxiety and huddle behavior, respectively.		7月25日（木）15:10～15:25　第9会場（朱鷺メッセ　3F　306+307） 1O-09a1-3 島回における神経細胞は社会性行動に関与する Isamu Miura（三浦勇）¹，Nobuhiro Nakai（中井信裕）¹，Nobuo Kunori（九里信夫）¹，Takakazu Kawamata（川俣貴一）²，Masaaki Sato（佐藤正晃）^1,3，Toru Takumi（内匠透）¹ ¹理研CBS 精神生物学 ²東京女子医大院医 ³埼玉大院理工学研究科 Object: The neural activity of the insular cortex (AI) is thought to be involved in social behavior. Since there is a methodological difficulty in measurement of the AI activity at cellular-resolution, it remains unclear how the neurons respond or contribute to social behavior. By using a microendoscopic system that allows to perform functional imaging at cellular resolution, we imaged the neural activities in the AI of mice during social behavior and we examined the change of social behavior by optogenetic manipulation of the AI neurons. Method: First, we utilized microendoscopic calcium imaging for real time measurement of neural activities in the AI of freely moving mice. For calcium imaging, a gradient index lens was implanted into the AI area and the activity of excitatory neurons was visualized by expressing the green fluorescent calcium indicator protein, GCaMP6f, using AAV vector system. Social behavior was tested in a home cage. While a subject mouse freely moved, a stranger mouse and a toy object, as a control, were alternately put in the cage. We monitored social behavior of the subject mice and analyzed neural activities in the AI according to different behavioral indices (interaction with the stranger or object, touch with wall, running, grooming and so on). Next, we assessed function of the AI neurons for the social behavior by optogenetically changing the neural activities. Optic cannulas were implanted into the bilateral AI area and channelrhodopsin2 and Jaws, a red-shifted cruxhalorhodopsin were expressed in the AI using AAV vector system for optogenetic excitation and inhibition, respectively. We monitored social behavior of the subject mice under the light on and off conditions. Result: We measured the neural activities of over 200 cells in the AI from seven subject mice. We found that around 10 % of neurons in the AI showed enhanced activity especially during social behavior in a home cage. We found that the time of social interaction was decreased by optogenetic inhibition of the AI using Jaws, indicating that the neural activities of the AI are necessary to retain social interaction behavior. Conclusion: Our finding suggests that around10 % of the AI neurons encodes social interaction behavior.

7月25日（木）15:25～15:40　第9会場（朱鷺メッセ　3F　306+307） 1O-09a1-4 反発性ガイダンス因子FLRT2による社会性行動制御 Satoru Yamagishi（山岸覚）¹，Fumihiro Eto（衞藤史博）²，Yo Shinoda（篠田陽）³，Shuhei Ogawa（小川修平）⁴，Ikuko Yao（矢尾育子）²，Keizo Takao（高雄啓三）^5,6，Tsuyoshi Miyakawa（宮川剛）^5,7，Kohji Sato（佐藤康二）¹ ¹浜松医大医解剖（器官組織） ²浜松医大メディカルフォトニクス研究センター基盤光医学研究部門光イメージング研究室 ³東京薬科大薬公衆衛生 ⁴東京理科大生命医科学研究所実験動物学研究部門 ⁵自然科学研究機構生理学研究所行動・代謝分子解析センター ⁶富山大学研究推進機構研究推進総合支援センター ⁷藤田医大総合医科学研究所 During cortical development, migrating neurons and pathfinding axons are guided by molecular cues within the extracellular matrix or on the surface of ambient cells. These cues are interpreted as attractive or repulsive, depending on the set of receptors and signal transducers the cell expresses. We previously identified fibronectin leucine-rich transmembrane protein (FLRT) family as ligand of Unc5 proteins, a well-known Netrin receptors. FLRT2 is expressed in the cortical plate (CP) and inhibited migration of Unc5D+ cells in the subventricular zone (SVZ). The upper layer neurons in FLRT2 mutant mice showed earlier migration to CP, indicating repulsive function of FLRT2. However, the behavioral phenotype of FLRT2 deficient mutant mice was unclear. Here, we comprehensively analyzed behaviors of Emx1 cre induced- FLRT2 conditional knock-out mice using the test battery, including rotor-rod, T-maze, Barns maze, fear conditioning, prepulse inhibition, tail suspension, forced swim, object location test, pattern separation test, open-field, light/dark transition, elevated plus maze, hot plate test and social interaction test. Among these tests, we found that mutant mice showed significant enhancement of anxiety-like behaviors (light/dark transition and elevated maze), pain sensitivity (hot plate) and social interaction. Furthermore, exploratory locomotor activity was decreased (open-field and Y-maze tests). Next, we analyzed the amino acids contents in the brain by matrix-assisted laser desorption/ionisation (MALDI) based imaging mass spectrometry. We found that serotonin content in the forebrain of FLRT2 cKO is higher than control mice. Furthermore, we analyzed the morphological change in primary cultured neurons. Interestingly, neurons from FLRT2 mutant harbored longer axons. These results suggest that mis-connecting neurons might affect the behaviors of FLRT2 deficient mice such as social interaction and anxiety-like behaviors.