Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum.

Transcriptional and anatomical diversity of medium spiny neurons in the primate striatum.
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DOI:
10.1016/j.cub.2021.10.015
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发表时间:
2021-12-20
期刊:
影响因子:
9.2
通讯作者:
Stauffer, William R.
Stauffer, William R.
中科院分区:
生物学1区
文献类型:
--
作者:
He, Jing;Kleyman, Michael;Chen, Jianjiao;Alikaya, Aydin;Rothenhoefer, Kathryn M.;Ozturk, Bilge Esin;Wirthlin, Morgan;Bostan, Andreea C.;Fish, Kenneth;Byrne, Leah C.;Pfenning, Andreas R.;Stauffer, William R.

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中型多棘神经元 (MSN) 构成了纹状体神经元的绝大多数,也是多巴胺奖赏信号和功能多样的皮质基底神经节回路之间的主要界面。这些回路中的信息处理取决于不同的 MSN 类型——传统上根据其投射目标或多巴胺受体表达来定义的细胞类型。单细胞转录研究揭示了 MSN 异质性比传统电路模型预测的更大,但灵长类纹状体中的转录景观仍然未知。在这里,我们着手建立恒河猴 MSN 亚型的分子定义,并探索转录定义的亚型与纹状体解剖细分之间的关​​系。我们的结果表明至少有九种MSN亚型,包括与纹状体和基质区室相关的背侧纹状体亚型、与伏隔核壳和嗅结节相关的腹侧纹状体亚型,以及仅限于腹侧纹状体中富含μ阿片受体的岛的MSN样细胞类型。尽管每个亚型是通过基因表达的不连续性来划分的,但亚型内的连续变化定义了与解剖位置和潜在的功能专业化相对应的梯度。这些结果为在灵长类纹状体中实现细胞类型特异性转基因奠定了基础,并为研究电路特异性信息处理提供了蓝图。
Medium spiny neurons (MSNs) constitute the vast majority of striatal neurons and the principal interface between dopamine reward signals and functionally diverse cortico-basal ganglia circuits. Information processing in these circuits is dependent on distinct MSN types – cell types that are traditionally defined according to their projection targets or dopamine receptor expression. Single cell transcriptional studies have revealed greater MSN heterogeneity than predicted by traditional circuit models, but the transcriptional landscape in the primate striatum remains unknown. Here, we set out to establish molecular definitions for MSN subtypes in Rhesus monkeys, and to explore the relationships between transcriptionally defined subtypes and anatomical subdivisions of the striatum. Our results suggest at least nine MSN subtypes, including dorsal striatum subtypes associated with striosome and matrix compartments, ventral striatum subtypes associated with the nucleus accumbens shell and olfactory tubercle, and an MSN-like cell type restricted to μ-opioid receptor rich islands in the ventral striatum. Although each subtype was demarcated by discontinuities in gene expression, continuous variation within subtypes defined gradients corresponding to anatomical locations and, potentially, functional specializations. These results lay the foundation for achieving cell-type-specific transgenesis in the primate striatum and provide a blueprint for investigating circuit specific information processing.
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