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Publication : Histamine H(1) receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice.

First Author  Cheng L Year  2024
Journal  Nat Commun Volume  15
Issue  1 Pages  5805
PubMed ID  38987240 Mgi Jnum  J:360199
Mgi Id  MGI:7665667 Doi  10.1038/s41467-024-50042-4
Citation  Cheng L, et al. (2024) Histamine H(1) receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice. Nat Commun 15(1):5805
abstractText  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 H(1) receptor (H(1)R) exerts critical and intricate effects on fear memory, the role of H(1)R is still not clarified. Here, we show that deletion of H(1)R 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. H(1)R in cholinergic neurons mediates the contextual fear retrieval rather than consolidation by decreasing acetylcholine release pattern in DG. Furthermore, selective knockdown of H(1)R in the MS is sufficient to enhance contextual fear memory by manipulating the retrieval-induced neurons in DG. Our results suggest that H(1)R in MS cholinergic neurons is critical for contextual fear retrieval, and could be a potential therapeutic target for individuals with fear-related disorders.
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