High impulsivity characterizes a myriad of neuropsychiatric diseases, and identifying targets for neuropharmacological intervention to reduce impulsivity could reveal transdiagnostic treatment strategies. Motor impulsivity (impulsive action) reflects in part the failure of "top-down" executive control by the medial prefrontal cortex (mPFC). The present study profiled the complete set of mRNA molecules expressed from genes (transcriptome) in the mPFC of male, outbred rats stably expressing high (HI) or low (LI) motor impulsivity based upon premature responses in the 1-choice serial reaction time (1-CSRT) task. RNA-sequencing identified expression of 18 genes that was higher in the mPFC of HI vs. LI rats. Functional gene enrichment revealed that biological processes related to calcium homeostasis and G protein-coupled receptor (GPCR) signaling pathways, particularly glutamatergic, were overrepresented in the mPFC of HI vs. LI rats. Transcription factor enrichment identified mothers against decapentaplegic homolog 4 (SMAD4) and RE1 silencing transcription factor (REST) as overrepresented in the mPFC of HI rats relative to LI rats, while in silico analysis predicted a conserved SMAD binding site within the voltage-gated calcium channel subunit alpha1 E (CACNA1E) promoter region. qRT-PCR analyses confirmed that mRNA expression of CACNA1E, as well as expression of leucyl and cystinyl aminopeptidase (LNPEP), were higher in the mPFC of HI vs. LI rats. These outcomes establish a transcriptomic landscape in the mPFC that is related to individual differences in motor impulsivity and propose novel gene targets for future impulsivity research.

中文翻译：

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固有的运动冲动与大鼠内侧前额叶皮层中的特定基因目标相关联。

高冲动性是无数神经精神疾病的特征，而确定降低冲动性的神经药理干预目标可以揭示转诊治疗策略。运动冲动（冲动作用）部分反映了内侧前额叶皮层（mPFC）的“自上而下”执行控制的失败。本研究概述了在1-choice系列反应时间中基于过早反应稳定稳定表达高（HI）或低（LI）运动冲动的雄性，近交雄性大鼠mPFC中从基因（转录组）表达的mRNA分子的完整集合（ 1-CSRT）任务。RNA测序确定了HI与LI大鼠的mPFC中18个基因的表达较高。功能基因富集显示，与HI大鼠相比，LI大鼠的mPFC中与钙稳态和G蛋白偶联受体（GPCR）信号通路（尤其是谷氨酸能通路）有关的生物学过程过度表达。转录因子富集鉴定出母亲对抗十足瘫痪同系物4（SMAD4）和RE1沉默转录因子（REST）在HI大鼠的mPFC中相对于LI大鼠而言过高，而计算机分析预测电压门控钙通道内的SMAD结合位点是保守的亚基α1E（CACNA1E）启动子区域。qRT-PCR分析证实，HI大鼠的mPFC中CACNA1E的mRNA表达以及亮氨酰和半胱氨酰氨肽酶（LNPEP）的表达均高于LI大鼠。