Stevenson Carl W, Marsden Charles A, Mason Rob
School of Biomedical Sciences, University of Nottingham, Nottingham, UK.
Brain Res. 2008 Feb 8;1193:43-50. doi: 10.1016/j.brainres.2007.11.062. Epub 2007 Dec 8.
Maternal separation (MS) during the neonatal period enhances stress responsivity in adulthood. The medial prefrontal cortex (mPFC) and the basolateral amygdala (BLA) are involved in coordinating various stress responses. Evidence indicates that MS reduces benzodiazepine and GABA(A) receptor expression in these regions, although their effects on neuronal function in the mPFC and the BLA remain unknown. The present study was conducted to assess the effects of MS on neuronal activity in the mPFC and BLA in response to the benzodiazepine receptor partial inverse agonist N-methyl-beta-carboline-3-carboxamide (FG-7142). Rat pups were subjected to MS (360 min), brief handling (H; 15 min) or standard animal facility rearing (AFR) on postnatal days 2-14. In adult males, in vivo electrophysiology under isoflurane anesthesia was used to conduct acute recordings of extracellular unit activity in response to systemic FG-7142 administration. Animals subjected to H showed significantly increased basal mPFC activity compared to MS and AFR animals. There were no differences in basal BLA activity between the early rearing groups. In response to FG-7142, MS animals showed significantly attenuated mPFC activity compared to H animals and a nonsignificant trend towards attenuated mPFC activity compared to AFR animals. In contrast to mPFC, MS animals showed significantly potentiated FG-7142-induced activity in the BLA, compared to both H and AFR animals. These findings indicate that MS induces functionally relevant alterations in corticolimbic GABA(A) receptor signaling. Given that FG-7142 mimics several behavioral and physiological effects of stress, these results may also model stress-induced corticolimbic dysfunction caused by early life stress.
新生儿期的母婴分离（MS）会增强成年后的应激反应性。内侧前额叶皮质（mPFC）和基底外侧杏仁核（BLA）参与协调各种应激反应。有证据表明，MS会降低这些区域中苯二氮䓬和GABA(A)受体的表达，尽管它们对mPFC和BLA中神经元功能的影响尚不清楚。本研究旨在评估MS对mPFC和BLA中神经元活动的影响，这些神经元活动是对苯二氮䓬受体部分反向激动剂N-甲基-β-咔啉-3-甲酰胺（FG-7142）的反应。在出生后第2 - 14天，将幼鼠进行母婴分离（360分钟）、短暂处理（H；15分钟）或标准动物设施饲养（AFR）。对于成年雄性大鼠，在异氟烷麻醉下采用体内电生理学方法，对全身给予FG-7142后的细胞外单位活动进行急性记录。与母婴分离和标准动物设施饲养的动物相比，接受短暂处理的动物表现出基础mPFC活动显著增加。早期饲养组之间的基础BLA活动没有差异。与短暂处理组动物相比，母婴分离组动物在给予FG-7142后，mPFC活动显著减弱；与标准动物设施饲养组动物相比，母婴分离组动物的mPFC活动有减弱的趋势，但不显著。与mPFC相反，与短暂处理组和标准动物设施饲养组动物相比，母婴分离组动物在BLA中表现出FG-7142诱导的活动显著增强。这些发现表明，母婴分离会诱导皮质边缘GABA(A)受体信号传导发生功能相关的改变。鉴于FG-7142模拟了应激的几种行为和生理效应，这些结果也可能模拟了早期生活应激引起的应激诱导的皮质边缘功能障碍。
