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出生后触须皮层中神经元细胞类型发育和可塑性的分子状态。

Molecular states underlying neuronal cell type development and plasticity in the postnatal whisker cortex.

作者信息

Butrus Salwan, Monday Hannah R, Yoo Christopher J, Feldman Daniel E, Shekhar Karthik

机构信息

Department of Chemical and Biomolecular Engineering, University of California, Berkeley, Berkeley, California, United States of America.

Department of Neuroscience, University of California, Berkeley, Berkeley, California, United States of America.

出版信息

PLoS Biol. 2025 May 14;23(5):e3003176. doi: 10.1371/journal.pbio.3003176. eCollection 2025 May.

Abstract

Mouse whisker somatosensory cortex (wS1) is a major model system to study the experience-dependent plasticity of cortical neuron physiology, morphology, and sensory coding. However, the role of sensory experience in regulating neuronal cell type development and gene expression in wS1 remains poorly understood. We assembled a transcriptomic atlas of wS1 during postnatal development comprising 45 molecularly distinct neuronal types that can be grouped into eight excitatory and four inhibitory neuron subclasses. Between postnatal day (P) 12, the onset of active whisking, and P22, when classical critical periods close, ~ 250 genes were regulated in a neuronal subclass-specific fashion when whisker experience was normal. At the resolution of neuronal types, only the composition of layer (L) 2/3 glutamatergic neurons, but not other neuronal types, changed substantially between P12 and P22. These postnatal compositional changes in L2/3 neuronal types resemble those observed previously in the primary visual cortex (V1), and the temporal gene expression changes were also highly conserved between the regions. Unlike V1, however, cell type maturation in wS1 is not substantially dependent on sensory experience, as 10-day full-face whisker deprivation from P12 to P22 did not influence the transcriptomic identity nor composition of L2/3 neuronal types. A one-day competitive whisker deprivation protocol from P21 to P22 also did not affect cell type identity but induced moderate changes in plasticity-related gene expression. Thus, developmental maturation of cell types is similar in V1 and wS1, but sensory deprivation minimally affects cell type development in wS1.

摘要

小鼠触须体感皮层(wS1)是研究皮层神经元生理学、形态学和感觉编码中经验依赖性可塑性的主要模型系统。然而,感觉经验在调节wS1中神经元细胞类型发育和基因表达方面的作用仍知之甚少。我们构建了一个出生后发育期间wS1的转录组图谱,其中包含45种分子上不同的神经元类型,可分为八个兴奋性和四个抑制性神经元亚类。在出生后第(P)12天(主动触须运动开始)到P22天(经典关键期结束)之间,当触须经验正常时,约250个基因以神经元亚类特异性方式受到调控。在神经元类型的分辨率下,只有第2/3层谷氨酸能神经元的组成在P12和P22之间发生了显著变化,而其他神经元类型则没有。第2/3层神经元类型的这些出生后组成变化类似于先前在初级视觉皮层(V1)中观察到的变化,并且区域之间的时间基因表达变化也高度保守。然而,与V1不同的是,wS1中的细胞类型成熟在很大程度上不依赖于感觉经验,因为从P12到P22进行10天的全脸触须剥夺并不影响第2/3层神经元类型的转录组特征和组成。从P21到P22进行一天的竞争性触须剥夺方案也不影响细胞类型特征,但会诱导可塑性相关基因表达的适度变化。因此,V1和wS1中细胞类型的发育成熟相似,但感觉剥夺对wS1中细胞类型发育的影响最小。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5fa8/12119026/4cadcb56118d/pbio.3003176.g001.jpg

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