Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex
Social Isolation During the Critical Period Reduces Synaptic and Intrinsic Excitability of a Subtype of Pyramidal Cell in Mouse Prefrontal Cortex
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DOI：
10.1093/cercor/bhx010
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发表时间：
2018-03-01
期刊：
影响因子：
3.7
通讯作者：
Kishimoto, Toshifumi
中科院分区：
文献类型：
--
作者：
Yamamuro, Kazuhiko;Yoshino, Hiroki;Kishimoto, Toshifumi
青少年的社会经验对于前脑区域的功能发育至关重要，尤其是前额皮质（PFC）。我们之前报道过断奶后两周的社会隔离会导致前额皮质功能障碍和髓鞘形成不足。然而，社会隔离对 PFC 神经元回路生理特性的影响仍不清楚。由于隔离导致的髓鞘形成不足在内侧 PFC (mPFC) 深层很突出，因此我们重点关注 mPFC 中的 2 种类型的第 5 层锥体细胞：突出的 h 电流 (PH) 细胞和不突出的 h 电流 (non-PH) 细胞。我们发现断奶后两周的社会隔离会导致动作电位特性的特定恶化和 PH 细胞的兴奋性突触输入的减少。社会隔离对 PH 细胞的影响，包括功能性谷氨酸突触和 α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/N-甲基-d-天冬氨酸电荷比的减少，是断奶后 2 周和 mPFC 特有的。我们得出的结论是，青少年的社会经验在 mPFC 中第 5 层锥体细胞亚型的功能发育中起着至关重要的作用。由于这些神经元投射到皮质下结构，关键时期社交经验的缺乏可能会导致 mPFC 和皮质下目标之间的神经回路不成熟。
Juvenile social experience is crucial for the functional development of forebrain regions, especially the prefrontal cortex (PFC). We previously reported that social isolation for 2 weeks after weaning induces prefrontal cortex dysfunction and hypomyelination. However, the effect of social isolation on physiological properties of PFC neuronal circuit remained unknown. Since hypomyelination due to isolation is prominent in deep-layer of medial PFC (mPFC), we focused on 2 types of Layer-5 pyramidal cells in the mPFC: prominent h-current (PH) cells and nonprominent h-current (non-PH) cells. We found that a 2-week social isolation after weaning leads to a specific deterioration in action potential properties and reduction in excitatory synaptic inputs in PH cells. The effects of social isolation on PH cells, which involve reduction in functional glutamatergic synapses and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/N-methyl-d-aspartate charge ratio, are specific to the 2 weeks after weaning and to the mPFC. We conclude that juvenile social experience plays crucial roles in the functional development in a subtype of Layer-5 pyramidal cells in the mPFC. Since these neurons project to subcortical structures, a deficit in social experience during the critical period may result in immature neural circuitry between mPFC and subcortical targets.