The effects of early life stress on the excitatory/inhibitory balance of the medial prefrontal cortex
The effects of early life stress on the excitatory/inhibitory balance of the medial prefrontal cortex
复制标题
早期生活压力对内侧前额叶皮层兴奋/抑制平衡的影响
DOI：
10.1016/j.bbr.2019.112306
复制
发表时间：
2020
期刊：
影响因子：
2.7
通讯作者：
Miki T.
中科院分区：
文献类型：
--
作者：
Ohta KI;Suzuki S;Warita K;Sumitani K;Tenkumo C;Ozawa T;Ujihara H;Kusaka T;Miki T.
众所周知，生命早期的不良环境条件会导致长期的社交缺陷，类似于在神经发育障碍患者中观察到的情况。然而，早期生活压力如何导致社交缺陷的机制尚不清楚。为了阐明发育过程中处于厌恶环境中如何影响社交能力，我们对经历过母亲分离（MS）的年轻成年雄性大鼠进行了各种分析，重点关注内侧前额叶皮层（mPFC）的兴奋性和抑制性（E/I）平衡及其与社交缺陷的关系。在我们的 MS 程序中，在出生后 2-20 天期间，部分幼崽与每只母鼠分开 3 小时，每天两次，然后在 9 周大时用于每次分析。我们发现 MS 主要减少 mPFC 中抑制性神经元的突触前和突触后蛋白表达，并减少 mPFC 中 GAD67 阳性中间神经元和抑制性突触的数量。此外，在三腔社交性和社交新颖性测试（3-CST）中，MS 损害了与社会认知相关的社会行为，而社交认知与 mPFC 密切相关。与这种社交缺陷相关，免疫组织学分析显示，暴露于 MS 的大鼠 mPFC 中的 c-fos 阳性细胞在 3-CST 期间减少。考虑到 mPFC 中的抑制性神经元在同步信息处理的神经激活中发挥作用，我们的研究结果表明，MS 诱导的与 mPFC 中细胞活动相关的 E/I 失衡会导致社会识别缺陷。
Aversive environmental conditions during early life are known to cause long-lasting social deficits, similar to those observed in patients with neurodevelopmental disorders. However, the mechanism of how early life stress can cause social deficits is not well understood. To clarify how being in an aversive environment during development affects sociability, we conducted various analyses focusing on the excitatory and inhibitory (E/I) balance in the medial prefrontal cortex (mPFC) and how it is related to social deficits, with young adult male rats that had been exposed to maternal separation (MS). In our MS procedure, part of the pups were separated from each dam for 3 h, twice a day, during postnatal days 2–20, and then were used for each analysis at 9 weeks old. We identified that MS mainly reduced pre- and post-synaptic protein expression of inhibitory neurons in the mPFC, and that decreased the number of GAD67-positive interneurons and inhibitory synapses in the mPFC. Furthermore, MS impaired social behavior related to social recognition, which is closely linked to the mPFC, in the three-chamber sociability and social novelty test (3-CST). With relation to this social deficit, immunohistological analysis revealed that c-fos-positive cells in the mPFC of rats exposed to MS decreased during the 3-CST. Considering that inhibitory neurons in the mPFC play a role in synchronizing neural activation for information processing, our findings demonstrate that MS-induced E/I imbalance associated with cell activity in the mPFC leads to deficits in social recognition.