Histamine H(1) receptor deletion in cholinergic neurons induces sensorimotor gating ability deficit and social impairments in mice.
Histamine H(1) receptor deletion in cholinergic neurons induces sensorimotor gating ability deficit and social impairments in mice.
复制标题
胆碱能神经元组胺 H1 受体缺失会导致小鼠感觉运动门控能力缺陷和社交障碍
DOI：
10.1038/s41467-021-21476-x
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发表时间：
2021-02-18
影响因子：
16.6
通讯作者：
Chen Z
中科院分区：
文献类型：
--
作者：
Cheng L;Xu C;Wang L;An D;Jiang L;Zheng Y;Xu Y;Wang Y;Wang Y;Zhang K;Wang X;Zhang X;Bao A;Zhou Y;Yang J;Duan S;Swaab DF;Hu W;Chen Z
精神分裂症的阴性症状是导致功能预后不良的重要原因，但其发病机制尚不清楚。在这里，我们发现，在基底前脑（BF）胆碱能神经元组胺H1受体（H1R）的表达减少精神分裂症患者的阴性症状。小鼠胆碱能神经元H1R基因缺失导致BF至前额叶皮质的胆碱能投射功能障碍，并形成感觉运动门控缺陷、社交障碍和快感缺乏样行为。这些行为缺陷可以通过重新表达H1R或通过BF中胆碱能神经元的化学激活来挽救。BF胆碱能神经元的直接化学发生抑制产生这样的行为缺陷，也增加了对hypermotorism的易感性。我们的研究结果表明，BF胆碱能神经元的H1R缺陷是关键的感觉运动门控缺陷，社会障碍和快感缺乏样行为。这一发现可能有助于理解精神分裂症阴性症状的遗传和生化基础。
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.
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影响因子：
19.9
作者：
Cannon TD
通讯作者：
Cannon TD
影响因子：
6.6
作者：
Fusar-Poli, Paolo;Papanastasiou, Evangelos;McGuire, Philip
通讯作者：
McGuire, Philip
影响因子：
5.3
作者：
Bloem, Bernard;Schoppink, Luc;Wouterlood, Floris G.
通讯作者：
Wouterlood, Floris G.
影响因子：
5.7
作者：
Higley MJ;Picciotto MR
通讯作者：
Picciotto MR
影响因子：
16.2
作者：
Ballinger EC;Ananth M;Talmage DA;Role LW
通讯作者：
Role LW