シンポジウム（Symposium）

Symposium Emerging roles of neuropeptides in emotional valence representation for survivial シンポジウム情動的価値を制御する神経ペプチドの新しい役割

7月25日（木）9:03～9:30　第3会場（朱鷺メッセ　2F　メインホールB） 1S03m-1 オキシトシンによる情動性の涙 Takefumi Kikusui（菊水健史）¹，Kaori Murata（村田香織）¹，Toshihiro Imada（今田敏博）²，Jin Kai（Kai Jin）²，Kazutaka Mogi（茂木一孝）¹，Miho Nagasawa（永澤美保）¹，Shigeru Nakamura（中村滋）²，Kazuo Tsubota（坪田一男）² ¹麻布大学獣医学部 ²慶応大学医学部眼科学教室 Maternal care is profoundly important for mammalian survival, and maternal behaviors can also be expressed by non-biological parents after experience with infants. One critical molecular signal for maternal behavior is oxytocin, released by hypothalamic paraventricular nucleus (PVN) and stimulates maternal care by activation of neurons in medial preoptic area of the mother. This maternal care stimulates pups' oxytocin release, resulted in enhancing the attachment behavior toward the mother. This oxytocin mediated positive loop has a fundamental role on forming bonding in the dyad in mammalian species. This loop also exists between dogs and humans, probably due to the co-evolutional process. The eye-gaze from dogs acts as an attachment signal, and stimulates oxytocin release. The higher oxytocin in the owner enhances care-giving to the dogs, and dogs show secretion of oxytocin. This oxytocin positive loop was not observed in wolves. Moreover, oxytocin stimulates emotional tear secretion in dogs when being reunited with the owners. In a mice model, oxytocin receptors were highly expressed in myoepithelial cells in the lacrimal gland and oxytocin stimulation increased Ca2+ oscillation. These results suggest that emotional tear can be modulated by an ancient hormone, oxytocin in mammals.		7月25日（木）9:30～9:57　第3会場（朱鷺メッセ　2F　メインホールB） 1S03m-2 Male aggression gated by TIP39 signaling in the medial amygdala Mumeko C Tsuda（Tsuda Mumeko C）^1,2，Brian Coleman（Coleman Brian）²，Maria Perica（Perica Maria）²，Jonathan Kuo（Kuo Jonathan）²，Ted B Usdin（Usdin Ted B）² ¹Uniformed Services University, Bethesda, Maryland, USA ²Section on Fundamental Neuroscience, National Institute of Mental Health, Bethesda, Maryland, USA Psychopathologies related to social interaction are a significant social problem. Therefore, it is important to understand the biopsychological and neurobiological processes underlying such disorders. Based on anatomical evidence that tuberoinfundibular peptide of 39 residues (TIP39) and its receptor, parathyroid hormone 2 receptor (PTH2R), may play a role in modulating social behaviors, we examined the contribution of TIP39 signaling to adult intermale social behaviors in male mice. Compared to wild-type, PTH2R knockout (P2RKO) male mice exhibited considerably increased investigatory behavior toward same sex adult mice in a social investigation test, decreased levels of aggression toward an intruder mouse in the resident-intruder test, and more submissive like behaviors in a social dominance tube test. PTH2R expressing neurons and TIP39 containing terminals on projections from subparafascicular thalamic neurons are abundant in the medial amygdala (MeA), a brain region known to play a role in regulating social behaviors. Using either a local receptor blockade with a virally expressed antagonist or the designer receptor exclusively activated by designer drug (DREADD) approach, we found that blocking PTH2Rs or transiently inhibiting PTH2R-expressing neurons in the MeA of male mice reduced aggression levels and increased submissive behaviors, reproducing the behavioral changes we found in P2RKO mice. Collectively, these findings suggest that TIP39 signaling via PTH2Rs in the MeA contributes to the regulation of intermale social behaviors and this work may lead to the identification of a specific circuit regulating intermale social behavior.

7月25日（木）9:57～10:24　第3会場（朱鷺メッセ　2F　メインホールB） 1S03m-3 侵害受容性扁桃体におけるCGRPのシナプス修飾 Yukari Takahashi（高橋由香里），Yuya Okutsu（奥津裕也），Kei Shinohara（篠原恵），Mariko Sugimoto（杉本真理子），Yae K Sugimura（杉村弥恵），Fusao Kato（加藤総夫）慈恵医大神経科学 In addition to the well-known role as a key region in expression of emotional behaviors, the amygdala is also known as a site of abundant expression of neuropeptides and the receptors. For example, the direct projection from the lateral parabrachial nucleus (LPB), which conveys nociceptive information from the spinal and trigeminal sensory systems, is rich in calcitonin gene-related peptide (CGRP), and the capsular part of the central amygdala (CeC), a target of this input, is plenteous in its binding sites and receptors. This anatomical organization suggests that CGRP would be released from the terminals of LPB fibers in the CeC in response to nociceptive inputs. However, its functional consequence remains largely undetermined. We challenged a hypothesis that the robust synaptic potentiation at the glutamate-mediated LPB-CeC synaptic transmission in various pain models might depend on the CGRP-mediated signaling. We made formalin-induced inflammatory pain model in CGRP-null mice. First, we evaluated the mechanical threshold at hindpaws 6 hr after formalin injection. Despite the inflammation was occurred at left hindpaw, the mechanical hypersensitivity appeared at both sides of hindpaw in wild-type mice. However, this phenomenon was not observed at CGRP-null mice. This result indicates that CGRP might play a key role for the CeA-related central pain regulation. Second, we recorded LPB-CeC excitatory synaptic transmission at the same timing after formalin injection. LPB-CeC synaptic potentiation occured in wild-type mice, however, CGRP-null mice didn't show that. This result suggests that CGRP would be essential for the expression of pain-induced synaptic plasticity in the LPB-CeC synapse. Third, to reveal the molecular background of the effect of CGRP on the LPB-CeC synaptic potentiation, we then examined the effect of exogenous CGRP in wild-type mice. We found that the application of CGRP increase NMDA current and the potentiation was inhibited by CGRP receptor blocker and PKA blocker. It is concluded that CGRP in the amygdala plays a key role in pain-induced LPB-CeC synaptic plasticity and the plasticity could also affect the descending pain modulation system.		7月25日（木）10:24～10:51　第3会場（朱鷺メッセ　2F　メインホールB） 1S03m-4 ニューロペプチドによる不快価値コーディングと感覚応答制御 Masato Tsuji（辻真人）¹，Kazuo Emoto（榎本和生）^1,2 ¹東京大学大学院理学系研究科生物科学専攻 ²東京大学ニューロインテリジェンス国際研究機構 Animals flexibly change how they respond to sensory stimuli according to their current inner states. Negative inner states induced by threat (i.e. anxiety) promote/suppress response to aversive/appetitive sensory stimuli (""aversive shift in sensory response""), presumably to maximize the chance of survival. Although a host of brain regions have been implicated in such inner states, how a multitude of sensory responses are coordinately regulated remains unknown. Recently, it has been reported that Drosophila also exhibits signs of inner state such as persistent hyperactivity, following threatening stimulation. This motivated us to explore the possibility that threatening stimulation to Drosophila also induces aversive shift in sensory response. Here, by developing a novel virtual reality paradigm, we report that mechanical stimulation promotes/suppresses subsequent visual aversion/attraction. We further identified a neuropeptide that is responsible for this aversive shift. Consistently, a population of neurons expressing this neuropeptide were found necessary and sufficient for the aversive shift in visual responses. Interestingly, activation of the same neurons resulted in real-time place aversion, indicating that these neurons not only induce aversive shift in the visual responses but encode negative valence. Together these data argue that mechanical stimulation aversively shifts visual responses via neuropeptidergic neurons that also encode negative valence. We propose that our findings open up a new avenue to understanding how negative inner state coordinately regulates multiple sensory responses.