<title_ja>Chemogenetic activation of histamine neurons promotes retrieval of forgotten object memory through perirhinal H2 receptor activation</title_ja> <title_en>ヒスタミン神経の化学遺伝学的な活性化は嗅周皮質のH2受容体活性化を介して忘却した物体記憶の想起を促進させる</title

2-B-P-025 <title_ja>Chemogenetic activation of histamine neurons promotes retrieval of forgotten object memory through perirhinal H2 receptor activation</title_ja> <title_en>ヒスタミン神経の化学遺伝学的な活性化は嗅周皮質のH2受容体活性化を介して忘却した物体記憶の想起を促進させる</title_en> 〇横井雄斗¹、久保絢女²、西村京華²、森下良一¹、南雅文²、野村洋^1,2 Yokoi Yuto¹, Ayame Kubo², Kyoka Nishimura², Yoshikazu Morishita¹, Masabumi Minami², Hiroshi Nomura^1,2 ¹名古屋市立大・院医・認知機能病態学寄付講座、²北海道大・院薬・薬理学研究室 ¹Dept. Cognitive Funct & Pathol., Grad. Sch. Med. Sci. Nagoya City Univ., ²Dept. Pharm., Grad. Sch. Pharm. Sci. Hokkaido Univ. Histamine within the central nervous system is a promising target for reactivating forgotten memories. We have previously demonstrated that histamine H₃ receptor inverse agonists enhance histamine release in the perirhinal cortex (PRh) and facilitate retrieval of forgotten object memories. Nevertheless, considering that histamine H₃ receptors are expressed in non-histaminergic neurons as well, it is plausible that other neurotransmitter systems might also be involved in memory recovery. This study directly tested the contribution of central histamine signaling to retrieval recovery. We virally targeted hM3Dq, the Gq-coupled excitatory designer receptor exclusively activated by designer drugs (DREADD), to histaminergic neurons in the tuberomammillary nucleus of HDC-Cre mice. One week after the training session of the novel object recognition task, mice underwent a test session where one familiar and one novel objects were presented. The pre-test injection of clozapine-N-oxide to the mice receiving AAV-DIO-hM3Dq increased discrimination between novel and familiar objects, indicating enhanced memory retrieval. This effect was blocked by intra-PRh infusions of ranitidine, a histamine H₂ receptor antagonist. These results indicate that chemogenetic activation of histamine neurons promotes memory retrieval through PRh H₂ receptor activation.