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腹腔基础前脑中的后交联动组胺H3受体,胆能神经元调节上下文恐惧记忆

Yanrong Zheng¹, Lishi Fan², Zhuowen Fang²

¹Department of Pharmacology and Department of Pharmacy of the Second Affiliated Hospital, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Basic Medical Sciences, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory of Neuropharmacology and Translational Medicine of Zhejiang Province, College of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310053, China.

|September 7, 2023

概括

针对特定脑细胞中的组胺H3受体 (H3R) 可以改变恐惧记忆. 胆固醇神经元内H3R的缺陷增强了上下文恐惧记忆检索,提供了新的治疗途径.

科学领域:

神经科学是一个神经科学.
药理学药理学是指药理学的学科.
分子生物学分子生物学

背景情况:

过于强烈的恐惧记忆会导致病态状况.
组胺H3受体 (H3R) 是中枢神经系统 (CNS) 疾病的潜在治疗点.
对于H3R在恐惧记忆处理中的特定作用尚不清楚.

研究的目的:

为了研究组胺H3受体 (H3R) 在腹底前脑 (vBF) 中的胆固醇神经元中在调节上下文恐惧记忆中的作用.
确定H3R在恐惧记忆中的功能的细胞类型特异性和亚细胞局部.

主要方法:

利用基因淘汰和化学遗传技术来操纵H3R表达和特定大脑区域的胆固醇神经元活动.
采用光敏感的罗多素-H3R融合蛋白来对H3R活动进行时空控制.
通过结行为分析评估了上下文和暗示的恐惧记忆检索.

主要成果:

胆固醇神经元中H3R的选择性缺陷,但不是谷氨酸神经元,增强了背景恐惧记忆检索.
基因淘汰或vBF胆能神经元的化学激活模仿增强的恐惧记忆.
重新表达H3R或抑制vBF胆能神经元挽救了增强的结.
在vBF胆固醇神经元中的 postsynaptic H3Rs,而不是海马中的 presynaptic H3Rs,对于调节上下文恐惧记忆至关重要.

结论:

组胺H3受体 (H3R) 在调节情境恐惧记忆方面发挥着至关重要的作用,通过腹基底前脑中的胆能神经元调节情境恐惧记忆.
细胞类型和亚细胞位置特定的H3R调制对于准病态恐惧记忆至关重要.
这些发现表明H3R是治疗与恐惧相关疾病的治疗干预的有希望的目标.

关键词:

科普:神经科学是什么意思背景恐惧记忆情境恐惧记忆药物目标是药物目标.恐惧记忆恐惧记忆组织胺H3受体的受体.创伤后应激障碍创伤后应激障碍

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