Histamine H1 receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice

Li Cheng, Ling Xiao, Wenkai Lin, Minzhu Li, Jiaying Liu, Xiaoyun Qiu, Menghan Li, Yanrong Zheng, Cenglin Xu, Yi Wang and Zhong Chen ()
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Li Cheng: Zhejiang Chinese Medical University
Ling Xiao: Zhejiang Chinese Medical University
Wenkai Lin: Zhejiang Chinese Medical University
Minzhu Li: Zhejiang Chinese Medical University
Jiaying Liu: Zhejiang Chinese Medical University
Xiaoyun Qiu: Zhejiang Chinese Medical University
Menghan Li: Zhejiang Chinese Medical University
Yanrong Zheng: Zhejiang Chinese Medical University
Cenglin Xu: Zhejiang Chinese Medical University
Yi Wang: Zhejiang Chinese Medical University
Zhong Chen: Zhejiang Chinese Medical University

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Fear memory is essential for survival and adaptation, yet excessive fear memories can lead to emotional disabilities and mental disorders. Despite previous researches have indicated that histamine H1 receptor (H1R) exerts critical and intricate effects on fear memory, the role of H1R is still not clarified. Here, we show that deletion of H1R gene in medial septum (MS) but not other cholinergic neurons selectively enhances contextual fear memory without affecting cued memory by differentially activating the dentate gyrus (DG) neurons in mice. H1R in cholinergic neurons mediates the contextual fear retrieval rather than consolidation by decreasing acetylcholine release pattern in DG. Furthermore, selective knockdown of H1R in the MS is sufficient to enhance contextual fear memory by manipulating the retrieval-induced neurons in DG. Our results suggest that H1R in MS cholinergic neurons is critical for contextual fear retrieval, and could be a potential therapeutic target for individuals with fear-related disorders.

Date: 2024
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DOI: 10.1038/s41467-024-50042-4

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