REM sleep-active hypothalamic neurons may contribute to hippocampal social-memory consolidation

Han Qin; Ling Fu; Tingliang Jian; Wenjun Jin; Mengru Liang; Jin Li; Qianwei Chen; Xinyu Yang; Haoran Du; Xiang Liao; Kuan Zhang; Rui Wang; Shanshan Liang; Jiwei Yao; Bo Hu; Shuancheng Ren; Chunqing Zhang; Yanjiang Wang; Zhian Hu; Hongbo Jia; Arthur Konnerth; Xiaowei Chen

doi:10.1016/j.neuron.2022.09.004

REM sleep-active hypothalamic neurons may contribute to hippocampal social-memory consolidation

Neuron. 2022 Dec 7;110(23):4000-4014.e6. doi: 10.1016/j.neuron.2022.09.004. Epub 2022 Oct 21.

Authors

Han Qin¹, Ling Fu², Tingliang Jian³, Wenjun Jin⁴, Mengru Liang⁵, Jin Li⁴, Qianwei Chen⁴, Xinyu Yang⁶, Haoran Du⁶, Xiang Liao⁶, Kuan Zhang⁴, Rui Wang⁴, Shanshan Liang⁴, Jiwei Yao⁶, Bo Hu⁷, Shuancheng Ren⁷, Chunqing Zhang⁷, Yanjiang Wang⁷, Zhian Hu⁷, Hongbo Jia⁸, Arthur Konnerth⁹, Xiaowei Chen¹⁰

Affiliations

¹ Center for Neurointelligence, School of Medicine, Chongqing University, Chongqing 400044, China; Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing 400038, China. Electronic address: qinhan@cqu.edu.cn.
² Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics-Huazhong University of Science and Technology, Key Laboratory for Biomedical Photonics of Ministry of Education, School of Engineering Sciences, Huazhong University of Science and Technology, Wuhan 430074, China.
³ Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing 400038, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China.
⁴ Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing 400038, China.
⁵ Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing 400038, China; Department of Anatomy, School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, China.
⁶ Center for Neurointelligence, School of Medicine, Chongqing University, Chongqing 400044, China.
⁷ Institute of Brain and Intelligence, Third Military Medical University, Chongqing 400038, China.
⁸ Advanced Institute for Brain and Intelligence, Guangxi University, Nanning 530004, China; Institute of Neuroscience and the Munich Cluster for Systems Neurology, Technical University of Munich, 80802 Munich, Germany; Brain Research Instrument Innovation Center, Suzhou Institute of Biomedical Engineering and Technology, Chinese Academy of Sciences, Suzhou 215163, China; Combinatorial NeuroImaging Core Facility, Leibniz Institute for Neurobiology, 39118 Magdeburg, Germany.
⁹ Advanced Institute for Brain and Intelligence, Guangxi University, Nanning 530004, China; Institute of Neuroscience and the Munich Cluster for Systems Neurology, Technical University of Munich, 80802 Munich, Germany.
¹⁰ Brain Research Center and State Key Laboratory of Trauma, Burns, and Combined Injury, Third Military Medical University, Chongqing 400038, China; Chongqing Institute for Brain and Intelligence, Guangyang Bay Laboratory, Chongqing 400064, China. Electronic address: xiaowei_chen@tmmu.edu.cn.

PMID: 36272414
DOI: 10.1016/j.neuron.2022.09.004

Abstract

The hippocampal CA2 region plays a key role in social memory. The encoding of such memory involves afferent activity from the hypothalamic supramammillary nucleus (SuM) to CA2. However, the neuronal circuits required for consolidation of freshly encoded social memory remain unknown. Here, we used circuit-specific optical and single-cell electrophysiological recordings in mice to explore the role of sleep in social memory consolidation and its underlying circuit mechanism. We found that SuM neurons projecting to CA2 were highly active during rapid-eye-movement (REM) sleep but not during non-REM sleep or quiet wakefulness. REM-sleep-selective optogenetic silencing of these neurons impaired social memory. By contrast, the silencing of another group of REM sleep-active SuM neurons that projects to the dentate gyrus had no effect on social memory. Therefore, we provide causal evidence that the REM sleep-active hypothalamic neurons that project to CA2 are specifically required for the consolidation of social memory.

Keywords: hippocampal CA2; hypothalamus; memory consolidation; rapid-eye-movement sleep; social memory; spatial memory; supramammillary nucleus.

MeSH terms

Animals
Memory Consolidation*
Mice
Sleep