Qin Pengwei, Zhao Wanting, Zhou Xiaoting, Guo Yiqing, Li Lanfang, Liu Zhiqiang, Shen Xiya, Yang Chunqing, Tang Xiaomei, Yu Dian, Zhu Mengzheng, Wu Shiping, Cheng Long, Yang Jiahao, Li Xinyan, Li Hao, Zhu Ling-Qiang, Jing Wei, Du Hui-Yun, Liu Dan, Lu Youming
Innovation Center for Brain Medical Sciences of the Ministry of Education, Huazhong University of Science and Technology, Wuhan 430030, China.
Department of Pathophysiology, School of Basic Medicine and Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Sci Adv. 2025 Jun 6;11(23):eadt5400. doi: 10.1126/sciadv.adt5400. Epub 2025 Jun 4.
Social investigation is a complex behavior essential for understanding the surrounding world and is impaired in some major neuropsychiatric disorders. Yet, little is known about whether and, if yes, how social investigation is encoded in a specific type of cortical neurons. Here, we generated a computer vision tool to track social behavior of naïve mice and categorized them as high versus low social states. We integrated a genetically guided TRAP2 strategy with single-cell Ca image and found that activity dynamics of serotonin receptor 2c (Htr2c)-expressing neurons in the prelimbic cortical layer 5 encode high social states. We uncovered a long noncoding RNA Lrhcn1 that controls Hcn1 transcription and regulates ensemble activity of Htr2c neurons, and this regulation motivates social investigation. Htr2c neurons directly and functionally project to nitric oxide synthase (Nos1) neurons in the hypothalamic nucleus. Gain- and loss-of function studies demonstrated that this projection specifically processes socially conveyed information.
社会调查是一种对于理解周围世界至关重要的复杂行为，并且在一些主要的神经精神疾病中会受到损害。然而，对于社会调查是否以及（如果是）如何在特定类型的皮质神经元中进行编码，我们却知之甚少。在这里，我们开发了一种计算机视觉工具来追踪未经验的小鼠的社会行为，并将它们分为高社交状态和低社交状态。我们将基因引导的TRAP2策略与单细胞钙成像相结合，发现前边缘皮质第5层中表达血清素受体2c（Htr2c）的神经元的活动动态编码高社交状态。我们发现了一种长链非编码RNA Lrhcn1，它控制Hcn1转录并调节Htr2c神经元的整体活动，并且这种调节促进了社会调查。Htr2c神经元直接且功能性地投射到下丘脑核中的一氧化氮合酶（Nos1）神经元。功能获得和功能丧失研究表明，这种投射专门处理社会传递的信息。
