卫星星形胶质细胞对纹状体胆碱能中间神经元和多巴胺释放的快速调节

Rapid modulation of striatal cholinergic interneurons and dopamine release by satellite astrocytes.

作者信息

Stedehouder Jeffrey, Roberts Bradley M, Raina Shinil, Bossi Simon, Liu Alan King Lun, Doig Natalie M, McGerty Kevin, Magill Peter J, Parkkinen Laura, Cragg Stephanie J

机构信息

Centre for Cellular and Molecular Neurobiology, Department of Physiology, Anatomy and Genetics, University of Oxford, Oxford, OX1 3PT, UK.

Oxford Parkinson's Disease Centre, University of Oxford, Oxford, OX1 3PT, UK.

出版信息

Nat Commun. 2024 Nov 19;15(1):10017. doi: 10.1038/s41467-024-54253-7.

Abstract

Astrocytes are increasingly appreciated to possess underestimated and important roles in modulating neuronal circuits. Astrocytes in striatum can regulate dopamine transmission by governing the extracellular tone of axonal neuromodulators, including GABA and adenosine. However, here we reveal that striatal astrocytes occupy a cell type-specific anatomical and functional relationship with cholinergic interneurons (ChIs), through which they rapidly excite ChIs and govern dopamine release via nicotinic acetylcholine receptors on subsecond timescales. We identify that ChI somata are in unexpectedly close proximity to astrocyte somata, in mouse and human, forming a "soma-to-soma" satellite-like configuration not typically observed for other striatal neurons. We find that transient depolarization of astrocytes in mouse striatum reversibly regulates ChI excitability by decreasing extracellular calcium. These findings reveal a privileged satellite astrocyte-interneuron interaction for striatal ChIs operating on subsecond timescales via regulation of extracellular calcium dynamics to shape downstream striatal circuit activity and dopamine signaling.

摘要

星形胶质细胞在调节神经回路方面所发挥的作用越来越受到重视,但其重要性却一直被低估。纹状体中的星形胶质细胞可通过控制轴突神经调质(包括γ-氨基丁酸和腺苷)的细胞外水平来调节多巴胺传递。然而,我们在此揭示,纹状体星形胶质细胞与胆碱能中间神经元(ChIs)存在一种细胞类型特异性的解剖学和功能关系,通过这种关系,它们能在亚秒级时间尺度上通过烟碱型乙酰胆碱受体快速兴奋ChIs并控制多巴胺释放。我们发现,在小鼠和人类中,ChI的胞体与星形胶质细胞的胞体意外地紧密相邻,形成了一种“体对体”的卫星样结构,这在其他纹状体神经元中并不常见。我们发现,小鼠纹状体中星形胶质细胞的短暂去极化通过降低细胞外钙水平可逆地调节ChI的兴奋性。这些发现揭示了一种特殊的卫星星形胶质细胞 - 中间神经元相互作用,即纹状体ChIs通过调节细胞外钙动力学在亚秒级时间尺度上发挥作用,以塑造下游纹状体回路活动和多巴胺信号传导。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7db8/11577008/c9503ea2b310/41467_2024_54253_Fig1_HTML.jpg

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