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基底前脑胆碱能神经元的全脑图谱揭示了不同亚型之间的长程相互输入-输出回路。

Whole-brain mapping of basal forebrain cholinergic neurons reveals a long-range reciprocal input-output loop between distinct subtypes.

作者信息

Chen Zhaonan, Liu Yanmei, Yang Yunqi, Wang Lizhao, Qin Meiling, Jiang Zhishan, Xu Min, Zhang Siyu

机构信息

Department of Ophthalmology, Songjiang Hospital and Songjiang Research Institute, Shanghai Key Laboratory of Emotions and Affective Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.

Department of Anatomy and Physiology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Sci Adv. 2025 May 30;11(22):eadt1617. doi: 10.1126/sciadv.adt1617.

Abstract

Basal forebrain cholinergic neurons (BFCNs) influence cognition and emotion through specific acetylcholine release in various brain regions, including the prefrontal cortices and basolateral amygdala (BLA). Acetylcholine release is controlled by distinct BFCN subtypes, modulated by excitatory and inhibitory inputs. However, the organization of the whole-brain input-output networks of these subtypes remains unclear. Here, we identified two distinct BFCN subtypes-BFCN and BFCN-innervating the anterior cingulate cortex (ACA) and BLA, each with unique distributions, electrophysiological properties, and projection patterns. Combining rabies-virus-assisted mapping and triple-plex RNAscope hybridization, we characterized their whole-brain input networks, identifying unique excitatory and shared inhibitory inputs for these subtypes. Moreover, our results reveal a long-range reciprocal input-output loop: BFCN neurons target the isocortex, their shared excitatory-input source, whereas BFCN neurons target shared inhibitory-input sources such as the striatum and pallidum, thus enabling dynamic interactions among these BFCN subtypes. Our study deepens understanding of cholinergic modulation in cognition and emotion and provides insights into their functional interactions.

摘要

基底前脑胆碱能神经元(BFCNs)通过在包括前额叶皮质和基底外侧杏仁核(BLA)在内的各个脑区特异性释放乙酰胆碱来影响认知和情绪。乙酰胆碱的释放由不同的BFCN亚型控制,受兴奋性和抑制性输入的调节。然而,这些亚型的全脑输入-输出网络的组织仍不清楚。在这里,我们鉴定出两种不同的BFCN亚型——支配前扣带回皮质(ACA)和BLA的BFCN和BFCN,它们各自具有独特的分布、电生理特性和投射模式。结合狂犬病病毒辅助图谱绘制和三重RNAscope杂交技术,我们对它们的全脑输入网络进行了表征,确定了这些亚型独特的兴奋性输入和共享的抑制性输入。此外,我们的结果揭示了一个长程相互输入-输出回路:BFCN神经元靶向等皮质,即它们共享的兴奋性输入源,而BFCN神经元靶向共享的抑制性输入源,如纹状体和苍白球,从而实现这些BFCN亚型之间的动态相互作用。我们的研究加深了对胆碱能在认知和情绪中调节作用的理解,并为它们的功能相互作用提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d695/12124396/16eaf65b65b4/sciadv.adt1617-f1.jpg

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