一般口演（Oral）

Oral Neural basis for aggression and affiliation 一般口演攻撃と親和の神経基盤

7月25日（木）15:40～15:55　第9会場（朱鷺メッセ　3F　306+307） 1O-09a2-1 社会的劣位行動は、内側手綱核腹側部ー脚間核回路による中央縫線核セロトニン神経細胞の活動抑制によって誘導される Miho Matsumata（松股美穂）¹，Kenzo Hirao（平尾顕三）¹，Takuma Kobayashi（小林琢磨）¹，Taku Sugiyama（杉山拓）¹，Yuki Kobayashi（小林祐樹）²，Huang J Arthur（Huang J Arthur）³，McHugh J Thomas（McHugh J Thomas）³，Shigeyoshi Itohara（糸原重美）²，Hitoshi Okamoto（岡本仁）¹ ¹理研CBS 意思決定回路動態 ²理研CBS 行動遺伝学 ³理研CBS 神経回路・行動生理学 The mammalian habenula is divided into the medial (MHb) and lateral parts with independent connectivity, and the MHb is subdivided into the dorsal (dMHb) and ventral (vMHb) subregions. Our group reported that silencing the lateral or medial subregion of dorsal habenula in zebrafish, corresponding to dMHb or vMHb in mammals, resulted in a higher tendency to lose or win fight, respectively. Following those results, we hypothesized that both the dMHb and vMHb in mice might relate to fighting behaviors but they work agonistically. Previous reports showed that the vMHb projects to the interpeduncular nucleus (IPN) and neurons in the vMHb include both glutamate and acetylcholine (ACh) as transmitters. We demonstrated that the mice in which ACh synthesis was selectively impaired in the vMHb (conditional choline acetyltransferase knock-out mice; cCKO mice) tended to win even against larger opponent mice (CD1 background wildtype mice) in tube test, a standard assay of defining which mice is dominant of two. On the other hand, when the mice was photo-activated in the vMHb-IPN pathway by micro-LED, they showed tendency to lose even against tamer opponent (C3H background wildtype mice). Next, we examined whether the median raphe (MnR) was also related to the social conflict behaviour or not, because it was reported that the MnR was a target nucleus of the IPN. First, by the use of the single-cell recording and optogenetic stimulation, we confirmed that the serotonergic (5HTergic) neurons of the MnR receive inputs from the γ-aminobutylic acid (GABA) neurons of the IPN, and that the vMHb, IPN and MnR are on the same pathway. Then, we examined the involvement of the MnR for social agonistic behavior. After inhibition type of designer receptors exclusively activated by designer drugs (DREADDs) was specifically expressed in the 5HT neurons of the MnR, those mice with clozapine N-oxide (CNO) injection behaved timidly even against C3H mice. Moreover, even the cCKO mice behaved submissively when the MnR was inhibited by DREADDs activation by CNO injection. Our findings suggest that the inhibition of the 5HT neurons in the MnR by the vMHb-IPN-pathway is responsible for the submissive behaviour of the loser. Now we are trying to examine whether the behaviour as the loser can be treated by inducing the MnR activation or not.		7月25日（木）15:55～16:10　第9会場（朱鷺メッセ　3F　306+307） 1O-09a2-2 内側視索前野に投射する扁桃体海馬野ニューロンは攻撃行動を誘発する Keiichiro Sato（佐藤圭一郎）^1,2，Kiyoshiro Fukui（福井清志郎）¹，Yumi Hamasaki（濱崎友美）¹，Kazuki Ito（伊藤和貴）¹，Kazunari Miyamichi（宮道和成）²，Masabumi Minami（南雅文）¹，Taiju Amano（天野大樹）¹ ¹北海道大学　大学院薬学研究院薬理学研究室 ²理化学研究所　生命機能科学研究センター比較コネクトミクス研究チーム Parental behavior is necessary to develop for mammalian infants. Early life stress, including inappropriate upbringing or absence of parenting increase the risk of major depression, posttraumatic stress disorder (PTSD), and other disorders. In addition, parental behavior influences the development of parental behavior for the next generation. The medial preoptic area (MPOA) is thought to be the most important region for parental behavior because lesions, cell-type specific ablation, and inactivation of the MPOA disrupt parental behavior. The MPOA projects to several regions such as the ventral tegmental area (VTA), medial amygdala (MeA) and periaqueductal grey (PAG), and each projection contribute to specific parental behavior. On the other hand, tracing studies reveal that the MPOA receives inputs from multiple regions such as amygdala, hypothalamus and cortex. Among them, we focused on the amygdalohippocampal area (AHi) projecting to the MPOA and expressing oxytocin receptor (OXTR), which is reported to play critical roles in social behavior supported by genetically removing studies and pharmacological studies. However, little is known about the function of AHi-MPOA projection and contribution of oxytocin in the AHi for social behavior. In this study, we found that MPOA-projection AHi neurons were activated by social contact with pups. TRIO method using rabies virus elucidated inputs to MPOA-projection AHi neurons. Next, we showed that oxytocin enhanced inhibitory response on these neurons. Finally, activation of MPOA-projection AHi neurons disrupted the expression of parental behavior.

7月25日（木）16:10～16:25　第9会場（朱鷺メッセ　3F　306+307） 1O-09a2-3 雌との社会行動経験によって起こる内側視索前野シナプス可塑的変化 Taiju Amano（天野大樹）^1,2，Kazuki Ito（伊藤和貴）¹，Haruka Uki（宇木遥）¹，Keiichiro Sato（佐藤圭一郎）¹，Yousuke Tsuneoka（恒岡洋右）³，Takashi Maejima（前島隆司）⁴，Takeshi Sakurai（櫻井武）⁵，Masabumi Minami（南雅文）¹，Kumi O Kuroda（黒田公美）² ¹北海道大院薬薬理 ²理化学研究所脳神経科学研究センター親和性社会行動研究チーム ³東邦大医解剖微細形態 ⁴金沢大院医薬保健医学系　統合神経生理 ⁵国際統合睡眠医科学研究機構 Whereas adult males polygyny mammals often show aggressive behavior toward non-offspring young animals, adaptation of polygyny males to young is widely observed. In male polygyny mice, social experiences with female and young cause the transition from aggressive to paternal behaviors even toward non-biological offspring. C57Bl/6J male require cohabitation with female until late gestation to show the behavioral transition from aggressive behavior to parental. However, neural mechanisms governing this behavioral transition through social experiences with female remain unknown. The medial preoptic area (MPOA) has been identified as one of the most important brain regions regulating parental behavior. Within the MPOA, the central part (cMPOA) appears to play a pivotal role in parental behavior because bilateral cMPOA lesions abolish this behavior and promote aggressive behavior in both maternal and paternal mice. Likewise, optogenetic activation of the MPOA in virgin male mice disrupted aggressive behavior However, the mechanisms to control the MPOA neuronal activities remained to be addressed. Previously, we reported that behavioral transition from aggressive to parental were initiated by the lesion of vomeronasal organ (VNO), which transmit olfactory information to the accessory olfactory bulb. Similar results were obtained in the experiment using genetically mutated mice with impaired vomeronasal signaling. Converging data using classical retrograde tracer study or recent mapping report using rabies virus indicate that accessary olfactory signaling mediates the medial amygdala (Me) and is transmitted to the MPOA. The present study addressees the efficacy of synaptic transmission from the cMPOA in virgin males, males that experienced mating but had not pup exposure, and males that experienced mating and pup exposure. We observed that inhibitory inputs from Me to cMPOA were suppressed ahead of pup delivery, leading to cMPOA disinhibition. Optogenetic inhibition of Me-cMPOA synapses promoted affiliative behavior toward pups. Together, these findings indicate that the synapse plastic change at the Me - cMPOA pathway observed in the male mice with social experiences with partner female has priming effects to shift the behavioral pattern toward pup.		7月25日（木）16:25～16:40　第9会場（朱鷺メッセ　3F　306+307） 1O-09a2-4 雌性行動の周期性を制御する神経基盤 Sayaka Inoue（井上清香）¹，Renzhi Yang（Yang Renzhi）³，Adarsh Tantry（Tantry Adarsh）¹，Chung-ha Davis（Davis Chung-ha）⁴，Taehong Yang（Yang Taehong）¹，Joseph R Knoedler（Knoedler R Joseph）¹，Yichao Wei（Wei Yichao）¹，Eliza L Adams（Adams L Eliza）⁴，Shivani Thombare（Thombare Shivani）¹，Samantha R Golf（Golf R Samantha）⁴，Rachael L Neve（Neve L Rachael）⁸，Marc Tessier-Lavigne（Tessier-Lavigne Marc）⁵，Jun B Ding（Ding B Jun）^6,7，Nirao M Shah（Shah M Nirao）^1,2 ¹Dept Psychiatry, Stanford University, Stanford, USA ²Dept Neurobiology, Stanford University, Stanford, USA ³Biology Program, Stanford University, Stanford, USA ⁴Neurosciences Program, Stanford University, Stanford, USA ⁵Dept Biology, Stanford University, Stanford, USA ⁶Dept Neurosurgery, Stanford University, Stanford, USA ⁷Dept Neurology, Stanford University, Stanford, USA ⁸Gene Delivery Technology Core, Massachusetts General Hospital, Cambridge, USA Behaviors are associated to the internal physiological state. In many species, females dramatically change their sexual behaviors along the state of ovulation. Females of many mammalian species, including mice, are sexually receptive exclusively during the estrus, ovulatory phase of the estrous cycle, while they are not receptive during other phases. In mice, the females are therefore receptive once every 5-6 days. Sex hormones such as estrogen and progesterone are required for both ovulation and female sexual behavior. Although central and peripheral mechanisms of ovulation is well characterized, neural circuit mechanisms underlying the estrus-associated change of the behavior is poorly understood. We have previously shown that progesterone receptor (PR) expressing neurons in the ventromedial hypothalamus (VMH) are essential for female sexual behavior. Targeted ablation of PR+ VMH neurons abolished female sexual behavior while it kept the estrous cycle intact. However, whether PR+ VMH neurons play a role in the estrus-associated change of female sexual behavior or they control the behavior independently from the estrus is unclear. Here we examine if PR+ VMH neurons link female sexual receptivity with the estrus phase. We find that activity of PR+ VMH is essential for ongoing female sexual behavior during estrus. Surprisingly however, calcium imaging via fiber photometry shows that these neurons are similarly active in females regardless of the estrous phase. Thus, female PR+ VMH neurons are active if the male attempts to mate even when the female is not in estrus and rejecting him. Consistent with this, further stimulation of these neurons in non-estrus phases does not elicit female sexual receptivity. In contrast to their estrous phase-invariant activity, we find that PR+ VMH neurons significantly strengthen their functional connections during estrus with a specific subset of projection target regions in the hypothalamus but not elsewhere. This functional strengthening during estrus is essential for female sexual receptivity because optogenetic inhibition of these connections specifically eliminates female sexual behavior. We will present these and related findings to demonstrate how PR+ VMH neurons play a critical role in associating an innate behavioral program, female sexual behavior, with internal physiological state.