Anatomy and Cell Biology Department, Oklahoma State University, Tulsa, OK, 74107, USA.
Booz Allen Hamilton, McLean, VA, USA.
Mol Neurobiol. 2021 Jan;58(1):348-361. doi: 10.1007/s12035-020-02125-8. Epub 2020 Sep 17.
Negative urgency is a facet of impulsivity associated with negative affect and risky behavior that may involve the amygdala. The current study determined if social isolation during development alters negative urgency and c-Fos activity in the basolateral amygdala (BLA). Female Sprague-Dawley rats were raised in an isolated condition (IC), a standard social condition (SC), or an enriched condition (EC) and then were tested for locomotor activity, novelty place preference, and negative urgency using a reward omission task. Following performance on the reward omission task, the brains were analyzed for c-Fos expression in Ca/calmodulin kinase II (CaMKII) and calbindin (CB) neurons, as well as in parvalbumin (PV) neurons associated with perineuronal nets (PNNs) in BLA. IC rats exhibited enhanced locomotion compared with both SC and EC rats, as well as enhanced novelty place preference compared with EC rats; only IC rats showed increased responding following omission of an expected reward (negative urgency). Following completion of the reward omission task, IC rats also displayed increased percent of c-Fos neurons in BLA associated with CaMKII, CB, and PV neurons compared with SC and EC rats. In IC rats, c-Fos activation in BLA occurred following the omission of an expected reward. Finally, IC rats displayed reduced PNN intensity associated with PV neurons compared with EC rats, but the percent of these neurons co-expressing c-Fos was greater in IC rats; SC rats were intermediate between IC and EC rats. Negative urgency was observed in IC rats, but not SC or EC rats. While multiple mechanisms are likely involved, this behavioral effect was associated with an isolation-induced increase in activity of excitatory neurons in BLA, as well as decreased PNN intensity surrounding GABAergic neurons in the same region.
消极紧迫感是冲动的一个方面，与消极情绪和冒险行为有关，可能涉及杏仁核。本研究旨在确定在发育过程中社会隔离是否会改变外侧杏仁核（BLA）中的消极紧迫感和 c-Fos 活性。雌性 Sprague-Dawley 大鼠在隔离条件（IC）、标准社会条件（SC）或丰富条件（EC）下饲养，然后进行运动活动、新奇位置偏好和使用奖励缺失任务进行消极紧迫感测试。在完成奖励缺失任务后，分析大脑中 Ca/calmodulin kinase II (CaMKII) 和钙结合蛋白 (CB) 神经元以及与 BLA 周围神经毡 (PNNs) 相关的副甲状腺素 (PV) 神经元中的 c-Fos 表达。与 SC 和 EC 大鼠相比，IC 大鼠表现出增强的运动活动，以及与 EC 大鼠相比增强的新奇位置偏好；只有 IC 大鼠在预期奖励缺失后表现出更高的反应（消极紧迫感）。完成奖励缺失任务后，与 SC 和 EC 大鼠相比，IC 大鼠的 BLA 中与 CaMKII、CB 和 PV 神经元相关的 c-Fos 神经元的百分比也增加。在 IC 大鼠中，BLA 中的 c-Fos 激活发生在预期奖励缺失之后。最后，与 EC 大鼠相比，IC 大鼠的 BLA 中与 PV 神经元相关的 PNN 强度降低，但这些神经元共表达 c-Fos 的百分比在 IC 大鼠中更高；SC 大鼠介于 IC 和 EC 大鼠之间。在 IC 大鼠中观察到消极紧迫感，但在 SC 或 EC 大鼠中没有观察到。虽然可能涉及多种机制，但这种行为效应与 BLA 中兴奋性神经元的隔离诱导活性增加以及同一区域中 GABA 能神经元周围 PNN 强度降低有关。
