一份关于组胺能神经元长程输入的全脑雄性小鼠图谱。

A whole-brain male mouse atlas of long-range inputs to histaminergic neurons.

作者信息

Lin Wenkai, Zhu Xinyan, Yu Xuemin, Fang Zhuowen, Xia Qinyan, Cheng Li, Li Menghan, Qiu Xiaoyun, Xu Lingyu, An Sile, Dou Chuhao, Zheng Yanrong, Hu Weiwei, Panula Pertti, Li Anan, Wang Yi, Luo Qingming, Chen Zhong

机构信息

Zhejiang Collaborative Innovation Center for the Brain Diseases with Integrative Medicine, Zhejiang Key Laboratory of Neuropsychopharmacology, School of Pharmaceutical Sciences & The First Affiliated Hospital, Zhejiang Chinese Medical University, Hangzhou, China.

Department of Pharmacology and Department of Pharmacy of the Second Affiliated Hospital, Key Laboratory of Medical Neurobiology of the Ministry of Health of China, School of Basic Medical Sciences, Zhejiang University School of Medicine, Hangzhou, China.

出版信息

Nat Commun. 2025 Aug 29;16(1):8092. doi: 10.1038/s41467-025-63394-2.

Abstract

The precise structural and functional characteristics of input circuits targeting histaminergic neurons remain poorly understood. Here, using a rabies virus retrograde tracing system combined with fluorescence micro-optical sectioning tomography, we construct a 3D monosynaptic long-range input atlas of male mouse histaminergic neurons. We identify that the hypothalamus, thalamus, pallidum, and hippocampus constitute major input sources, exhibiting diverse spatial distribution patterns and neuronal type ratios. Notably, a specific layer distribution pattern and co-projection structures of upstream cortical neurons are well reconstructed at single-cell resolution. As histaminergic system is classically involved in sleep-wake regulation, we demonstrate that the lateral septum (predominantly supplying inhibitory inputs) and the paraventricular nucleus of the thalamus (predominantly supplying excitatory inputs) establish monosynaptic connections, exhibiting distinct functional dynamics and regulatory roles in rapid-eye-movement sleep. Collectively, our study provides a precise long-range input map of mouse histaminergic neurons at mesoscopic scale, laying a solid foundation for future systematic study of histaminergic neural circuits.

摘要

靶向组胺能神经元的输入回路的精确结构和功能特征仍知之甚少。在此,我们使用狂犬病病毒逆行追踪系统结合荧光显微光学切片断层扫描技术,构建了雄性小鼠组胺能神经元的三维单突触远程输入图谱。我们发现下丘脑、丘脑、苍白球和海马体构成主要输入源,呈现出多样的空间分布模式和神经元类型比例。值得注意的是,上游皮质神经元的特定层分布模式和共投射结构在单细胞分辨率下得到了很好的重建。由于组胺能系统传统上参与睡眠-觉醒调节,我们证明外侧隔区(主要提供抑制性输入)和丘脑室旁核(主要提供兴奋性输入)建立了单突触连接,在快速眼动睡眠中表现出不同的功能动态和调节作用。总之,我们的研究提供了中尺度水平下小鼠组胺能神经元精确的远程输入图谱,为未来对组胺能神经回路的系统研究奠定了坚实基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1512/12397332/62e675606f87/41467_2025_63394_Fig1_HTML.jpg

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