公募シンポジウム

公募シンポジウム情動の変調を生み出す神経基盤

7月8日（土）　8:30-10:30　Room D 3SY①-1 報酬関連行動を導く神経分子基盤 Neural molecular substrates leading reward-related behaviors 永井　拓藤田医科大学　精神・神経病態解明センター　神経行動薬理学研究部門 Taku Nagai Div. of Behav. Neuropharmacol., ICBS, Fujita Health Univ., Toyoake, Japan Dopamine regulates emotional behaviors, including reward-related behaviors, through the mesolimbic dopaminergic pathway, which projects dopamine neurons from the ventral teg-mental area to the nucleus accumbens (NAc). Protein phosphorylation is critical for intracellular signaling pathways and physiological functions that are regulated by neurotransmitters in the brain. Previous studies demonstrated that dopamine stimulated the phosphorylation of intracellular substrates, such as receptors, ion channels, and transcription factors, to regulate neuronal excitability and synaptic plasticity through dopamine receptors. We also established a novel database called KANPHOS that provides information on phosphorylation signals downstream of monoamines identified by our kinase substrate screening methods, including dopamine, in addition to those reported in the literature. Recent advances in proteomics techniques have enabled us to clarify the mechanisms by which dopamine controls reward-related behaviors through signal pathways in the NAc. In this symposium, we discuss the intracellular phosphorylation signals regulated by dopamine in the behaviors.		7月8日（土）　8:30-10:30　Room D 3SY①-2 忌避行動学習におけるアセチルコリンの細胞内シグナル伝達機構 Acetylcholine-dependent Signal Transduction Leading to Aversive Learning 山橋　幸恵¹, 林　裕新², 毛利　彰宏³, Md.Omar Faruk⁴, 張　心健⁵, 坪井　大輔¹, 齋藤　尚亮⁶, 永井　拓⁵, 山田　清文⁷, 貝淵　弘三¹ 1. 藤田医科大学・医科学研究センター・神経・腫瘍のシグナル解析プロジェクト研究部門、豊明市、日本, 2. テキサス大学サウスウェスタン・メディカルセンター、ダラス、アメリカ, 3. 藤田医科大学・医療科学部・レギュラトリーサイエンス分野、豊明市、日本, 4. ダッカ大学、ダッカ、バングラディッシュ, 5. 藤田医科大学・精神・神経病態解明センター・行動薬理学部門、豊明市、日本, 6. 神戸大学・バイオシグナル総合研究センター・神経情報伝達学分野、神戸市、日本, 7. 名古屋大学・医学部病附属病院薬剤部・医療薬学講座、名古屋市、日本 Yukie Yamahashi¹, You-Hsin Lin², Akihiro Mouri³, Md.Omar Faruk⁴, Xinjian Zhang⁵, Daisuke Tsuboi¹, Naoaki Saito⁶, Taku Nagai⁵, Kiyofumi Yamada⁷, Kozo Kaibuchi¹ 1. Research Project for Neural and Tumor Signaling, Center for Medical Science, Fujita Health University, Toyoake, Japan, 2. University of Texas Southwestern Medical Center, Dallas, USA, 3. Department of Regulatory Science for Evaluation and Development of Pharmaceuticals and Devices, Fujita Health University, Toyoake, Japan, 4. University of Dhaka, Dhaka, Bangladesh, 5. Division of Behavioral Neuropharmacology, International Center for Brain Science, Fujita Health University, Toyoake, Japan, 6. Division of Signal Functions, Biosignal Research Center, Kobe University, Kobe, Japan, 7. Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Japan Acetylcholine (ACh) is critical for learning and memory, whose deficits is associated with Alzheimer’s disease (AD). Donepezil improves AD-associated learning deficits and memory loss, however, with side effects due to global activation of ACh receptors. Muscarinic receptor M1 (M1R), a key mediator of learning and memory, is considered as an alternative therapeutic target. The importance of targeting a specific pathway downstream of M1R has recently been recognized. Here, we demonstrate the identification of ACh-dependent signaling transduction in the striatum/nucleus accumbens leading to aversive learning, one of the outputs used for preliminary AD drug screening, by use of phosphoproteomic approach. By applying the identified ACh signaling pathway, we also demonstrate the intracellular mechanism of donepezil and M1R specific agonist in the hippocampus, in aim to clarify the molecular basis of ACh-dependent recognition memory. Elucidating signaling pathways beyond M1R holds important clues for understanding the molecular basis of ACh-based AD therapeutic drugs and for developing AD therapeutic strategies.

7月8日（土）　8:30-10:30　Room D 3SY①-3 攻撃行動の個体差における脳内免疫細胞の役割 Role of central immune cells in individual differences in aggression in male mice 高橋　阿貴筑波大学人間系 Aki Takahashi Faculty of Human Sciences, Univ. of Tsukuba, Tsukuba, Japan Human studies have shown correlations between immune system and aggression, but their causal links and mechanisms are still unknown. We used mouse model to examine the role of central cytokines on individual difference of aggressive behavior. Outbred ICR male mice show individual differences in aggressive behavior with three-fourth of mice exhibiting a spectrum of aggressive behavior (termed Aggressors: AGGs) and rest of mice showing no aggressive behavior (termed non-aggressors; NONs). We found that NONs showed higher level of interleukin 1β (IL-1β) in the dorsal raphe nucleus (DRN) compared to AGGs. Also, both pharmacological antagonism and genetic deletion of IL-1 receptors in the DRN caused an increase of aggressive behavior of in male mice, indicating that endogenous IL-1β in the DRN has suppressive effect on the expression of aggressive behavior. Cell sorting analysis showed that microglial cells in the DRN had the highest IL-1β mRNA expression compared to other cell types, and NON’s microglia showed higher IL-1β mRNA expressions than AGG’s microglia. These results suggest that the level of IL-1β production from microglia in the DRN produces individual differences in aggression. To examine the role of microglial cells in aggression, we are currently examining the effect of microglia depletion on aggressive behavior and those results will be discussed in this talk.		7月8日（土）　8:30-10:30　Room D 3SY①-4 社会性障害の回復機構における脳内オピオイドシステムバランスの役割 Role of the brain opioid system in regulation of social behavior 吾郷　由希夫広島大学　大学院医系科学研究科　細胞分子薬理学 Yukio Ago Dept. of Cell. Mol. Pharmacol., Grad. Sch. of Biomed. Health Sci., Hiroshima Univ., Hiroshima, Japan Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social impairments, communication difficulties and repetitive interests and behaviors. Additionally, individuals with ASD exhibit aberrant reactivity to sensory stimuli such as mechanical tactile stimuli. The opioid system is well known to relieve pain and underpin the rewarding properties of most drugs of abuse. Early animal research indicated a promising role for opioid modulation in other areas than pain, such as social bonding. Thereafter, accumulating evidence suggests that mu-opioid receptors (MORs) play an important role in modulating social behavior in humans and animals. We have examined the effects of MOR agonists on social behavioral deficits in a mouse model of ASD and found that low to moderate MOR activation without analgesic efficacy ameliorated social impairments. Low doses of MOR agonists activated neurons in the medial prefrontal cortex and nucleus accumbens, while high doses caused a further increase in neural activity in the periaqueductal gray matter, a main site of the opioidergic analgesia. These results suggests that low-dose MOR agonists improve social behavioral deficits through activation of specific brain regions and they might be useful for the symptomatic treatment of ASD. In this symposium, we would like to discuss about new treatment perspectives in ASD.