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空间转录组学揭示了调控慢性疼痛的小鼠前额叶皮层和神经元亚型的独特组织方式。

Spatial transcriptomics reveals the distinct organization of mouse prefrontal cortex and neuronal subtypes regulating chronic pain.

机构信息

Howard Hughes Medical Institute, Boston Children's Hospital, Boston, MA, USA.

Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, MA, USA.

出版信息

Nat Neurosci. 2023 Nov;26(11):1880-1893. doi: 10.1038/s41593-023-01455-9. Epub 2023 Oct 16.

DOI:10.1038/s41593-023-01455-9
PMID:37845544
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10620082/
Abstract

The prefrontal cortex (PFC) is a complex brain region that regulates diverse functions ranging from cognition, emotion and executive action to even pain processing. To decode the cellular and circuit organization of such diverse functions, we employed spatially resolved single-cell transcriptome profiling of the adult mouse PFC. Results revealed that PFC has distinct cell-type composition and gene-expression patterns relative to neighboring cortical areas-with neuronal excitability-regulating genes differently expressed. These cellular and molecular features are further segregated within PFC subregions, alluding to the subregion-specificity of several PFC functions. PFC projects to major subcortical targets through combinations of neuronal subtypes, which emerge in a target-intrinsic fashion. Finally, based on these features, we identified distinct cell types and circuits in PFC underlying chronic pain, an escalating healthcare challenge with limited molecular understanding. Collectively, this comprehensive map will facilitate decoding of discrete molecular, cellular and circuit mechanisms underlying specific PFC functions in health and disease.

摘要

前额叶皮层（PFC）是一个复杂的脑区，调节着从认知、情感和执行动作到疼痛处理等多种功能。为了解码这些多样化功能的细胞和回路组织，我们采用了空间分辨的成年小鼠 PFC 单细胞转录组谱分析。结果表明，与相邻的皮质区域相比，PFC 具有独特的细胞类型组成和基因表达模式——神经元兴奋性调节基因的表达不同。这些细胞和分子特征在 PFC 亚区进一步分离，暗示着 PFC 几种功能的亚区特异性。PFC 通过神经元亚型的组合投射到主要的皮质下靶点，这些组合以靶点内在的方式出现。最后，基于这些特征，我们在 PFC 中确定了与慢性疼痛相关的不同细胞类型和回路，慢性疼痛是一种呈上升趋势的医疗保健挑战，但其分子机制尚不清楚。总的来说，这幅综合图谱将有助于解码健康和疾病状态下 PFC 特定功能背后的离散分子、细胞和回路机制。

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