Histamine H1 receptor deletion in cholinergic neurons induces sensorimotor gating ability deficit and social impairments in mice

Li Cheng, Cenglin Xu, Lu Wang, Dadao An, Lei Jiang, Yanrong Zheng, Yixin Xu, Yi Wang, Yujing Wang, Kuo Zhang, Xiaodong Wang, Xiangnan Zhang, Aimin Bao, Yudong Zhou, Jingyu Yang, Shumin Duan, Dick F. Swaab, Weiwei Hu () and Zhong Chen ()
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Li Cheng: Zhejiang University
Cenglin Xu: Zhejiang University
Lu Wang: Zhejiang University
Dadao An: Zhejiang University
Lei Jiang: Zhejiang University
Yanrong Zheng: Zhejiang University
Yixin Xu: Zhejiang University
Yi Wang: Zhejiang University
Yujing Wang: Zhejiang University
Kuo Zhang: Shenyang Pharmaceutical University
Xiaodong Wang: Zhejiang University
Xiangnan Zhang: Zhejiang University
Aimin Bao: Zhejiang University
Yudong Zhou: Zhejiang University
Jingyu Yang: Shenyang Pharmaceutical University
Shumin Duan: Zhejiang University
Dick F. Swaab: Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences
Weiwei Hu: Zhejiang University
Zhong Chen: Zhejiang University

Nature Communications, 2021, vol. 12, issue 1, 1-17

Abstract: Abstract Negative symptoms in schizophrenia strongly contribute to poor functional outcomes, however its pathogenesis is still unclear. Here, we found that histamine H1 receptor (H1R) expression in basal forebrain (BF) cholinergic neurons was decreased in patients with schizophrenia having negative symptoms. Deletion of H1R gene in cholinergic neurons in mice resulted in functional deficiency of cholinergic projections from the BF to the prefrontal cortex and in the formation of sensorimotor gating deficit, social impairment and anhedonia-like behavior. These behavioral deficits can be rescued by re-expressing H1R or by chemogenetic activation of cholinergic neurons in the BF. Direct chemogenetic inhibition of BF cholinergic neurons produced such behavioral deficits and also increased the susceptibility to hyperlocomotion. Our results suggest that the H1R deficiency in BF cholinergic neurons is critical for sensorimotor gating deficit, social impairments and anhedonia-like behavior. This finding may help to understand the genetic and biochemical bases of negative symptoms in schizophrenia.

Date: 2021
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DOI: 10.1038/s41467-021-21476-x

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