On July 10, the research team led by Prof. Chen Zhong published a paper entitled Histamine H1 receptors in dentate gyrus-projecting cholinergic neurons of the medial septum suppress contextual fear retrieval in mice in Nature Communications. This study offers new insights into the mechanisms underlying fear memory and is expected to provide new targets for precise drug interventions in treating fear-related disorders.

Excessive fear memories can lead to various emotional and mental disorders, such as anxiety disorders, phobias, and post-traumatic stress disorder (PTSD). Currently, PTSD is primarily treated with psychological interventions, including cognitive behavioral therapy (CBT) and exposure therapy (ET). However, many patients fail to respond to these treatments and face a high risk of spontaneous recovery of fear memories. Additionally, there is no highly effective pharmacological treatment strategy for PTSD. Therefore, it is crucial to further elucidate the mechanisms of fear memory to identify new pharmacological strategies for treating fear-related disorders.

Prof. Chen Zhong’s research team focuses on the pathogenesis and drug targets of chronic brain diseases, with a significant emphasis on the role of the histaminergic nervous system in central nervous system functions and diseases. The team particularly investigates the precise role of different histamine receptors in specific neural circuits and cell types in the biology and pathogenesis of neuropsychiatric diseases (Adv Sci, 2024; Cell Rep, 2023; PNAS, 2023a,b; Curr Biol, 2022; Nat Commun, 2014, 2021; J Exp Med, 2021).

This study is the first to demonstrate that the histamine H₁ receptor (H₁R) on medial septal (MS) cholinergic neurons plays a crucial role in the retrieval phase of contextual fear memory. These findings provide new insights into the mechanisms of fear memory and identify a new target for precise drug interventions in the treatment of fear-related disorders.

The first author of the research is Cheng Li, Associate Researcher at ZCMU. The co-first authors are Xiao Ling, a master’s student at ZCMU, and Lin Wenkai, a postdoctoral fellow at the School of Pharmaceutical Sciences of ZCMU. Prof. Chen Zhong is the corresponding author.