研究人员首次绘出大脑行为守门人基底神经节细胞图谱，有望助解帕金森病
美国国立卫生研究院（NIH）11月12日宣布，在 NIH 大脑计划（BRAIN Initiative）支持下，科学家首次以空前细节全面绘出基底神经节图谱。基底神经节是把想法转化为行动的关键脑区，决定人如何执行有意识的身体动作、学习与专注。
这套图谱由大脑计划细胞图谱网络（BICAN）完成：研究人员对捐赠的死后人脑组织进行单细胞测序，再以先进成像技术把细胞的身份与活动对应到基底神经节内的三维坐标，编目数以百万计的细胞，覆盖成熟人脑与早期发育阶段，并延伸至非人灵长类、狨猴与小鼠的大脑。
研究者以图谱为蓝图重组自闭症患者的测序数据，发现纹状体某些细胞群可能出现扰动，提示自闭症机制可能涉及大脑深部回路，而不只是大脑皮层；另一项研究用基因开关在帕金森病小鼠模型中精准提升纹状体细胞的多巴胺前体水平，缓解了症状并减轻常见副作用的程度。
NIH 大脑计划主任 John Ngai 说，以这样的粒度呈现大脑，为理解基本脑功能以及神经、神经精神与物质使用障碍的细胞根源打开许多机会，这项工作已在为亨廷顿病、帕金森病等神经退行性疾病的靶向疗法铺路。相关27篇论文发表于《细胞》《神经元》等期刊，图谱与配套工具全部公开。
（来源：美国国立卫生研究院）
Researchers Map the Brain's Behavioral Gatekeeper for the First Time in NIH-Funded Atlas
The National Institutes of Health (NIH) announced on November 12 that scientists funded by the NIH BRAIN Initiative have comprehensively mapped the basal ganglia, a brain region critical for turning thoughts into actions, in unprecedented detail. The basal ganglia determines how we execute deliberate physical actions, learn and focus.
The atlas was produced by the BRAIN Initiative Cell Atlas Network (BICAN). Researchers performed single-cell sequencing on donated postmortem human brain tissue and used advanced imaging to link each cell's identity and activity to 3D coordinates in the basal ganglia, cataloguing millions of cells across the mature human brain and early development, as well as non-human primate, marmoset and mouse brains.
Using the atlas as a blueprint, one group reorganized sequencing data from people with autism and found potentially key disruptions in certain cell populations of the striatum, suggesting autism mechanisms may involve circuits deep in the brain, not only the cortex. Another study used a genetic enhancer switch to boost a dopamine precursor in striatum cells in mouse models of Parkinson's disease, alleviating symptoms while reducing the severity of common side effects.
John Ngai, director of the NIH BRAIN Initiative, said representing the brain at this level of granularity opens opportunities to understand basic brain function and the cellular underpinnings of neurologic, neuropsychiatric and substance use disorders, and is already paving the way toward targeted therapies for neurodegenerative disorders such as Huntington's and Parkinson's diseases. The collection of 27 papers appears in Cell, Neuron and sister journals, and the atlases and tools are publicly available.
(Source: National Institutes of Health)
来源：美国国立卫生研究院
发布：GSM·美国（发布链接）
图片来源：图：美国卫生与公众服务部总部大楼（国立卫生研究院上级机构）。GSM 固定图库照片。 / Photo: U.S. Department of Health and Human Services headquarters, parent department of NIH. GSM fixed image library.
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