Bhattacherjee, A., Djekidel, M.N., Chen, R. et al. 2019

Coordinated activity-induced transcriptional changes across multiple neuron subtypes of the prefrontal cortex (PFC) play a pivotal role in encoding and regulating major cognitive behaviors. Yet, the specific transcriptional programs in each neuron subtype remain unknown. Using single-cell RNA sequencing (scRNA-seq), here we comprehensively classified all unique cell subtypes in the PFC. We analyzed transcriptional dynamics of each cell subtype under a naturally adaptive and an induced condition. Adaptive changes during adolescence (between P21 and P60), a highly dynamic phase of postnatal neuroplasticity, profoundly impacted transcription in each neuron subtype, including cell type-specific regulation of genes implicated in major neuropsychiatric disorders. On the other hand, an induced plasticity evoked by chronic cocaine addiction resulted in progressive transcriptional changes in multiple neuron subtypes and became most pronounced upon prolonged drug withdrawal. Our findings lay a foundation for understanding cell type-specific postnatal transcriptional dynamics under normal PFC function and in neuropsychiatric disease states.<br><br>Full dataset also available here: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE124952

前额叶皮层（prefrontal cortex, PFC）内多种神经元亚型的协同活动诱导的转录改变，在编码与调控主要认知行为过程中发挥核心作用。然而，目前各神经元亚型的特异性转录程序仍未明确。本研究利用单细胞RNA测序（single-cell RNA sequencing, scRNA-seq）技术，对前额叶皮层内所有独特的细胞亚型进行了全面分类，并分析了自然适应与诱导两种状态下各细胞亚型的转录动态变化。青春期（出生后第21天至第60天）是产后神经可塑性高度活跃的阶段，此阶段发生的适应性变化对各神经元亚型的转录组产生了显著影响，包括对与主要神经精神疾病相关基因的细胞类型特异性调控。另一方面，慢性可卡因成瘾诱发的可塑性变化，会导致多种神经元亚型出现进行性转录改变，且在长期药物戒断后该变化最为显著。本研究的发现为理解正常前额叶皮层功能及神经精神疾病状态下细胞类型特异性的产后转录动态变化奠定了理论基础。

完整数据集可通过以下链接获取：https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE124952