Department of Psychiatry, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Department of Physiology I, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Cereb Cortex. 2018 Mar 1;28(3):998-1010. doi: 10.1093/cercor/bhx010.
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 α-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.
幼年时期的社交经历对大脑前额叶区域（prefrontal cortex，PFC），尤其是前额叶皮质（prefrontal cortex，PFC）的功能发育至关重要。我们之前的研究表明，断奶后两周的社交隔离会导致前额叶皮质功能障碍和少突胶质细胞发育不良。然而，社交隔离对前额叶皮质神经元回路的生理特性的影响尚不清楚。由于隔离引起的少突胶质细胞发育不良在 PFC 的深层（medial PFC，mPFC）中更为明显，因此我们重点研究了 mPFC 中的 2 种 5 层锥体神经元：具有明显 h 电流（h-current，h-current）的神经元和不具有明显 h 电流的神经元（nonprominent h-current，non-PH）细胞。我们发现，断奶后两周的社交隔离会导致动作电位特性的特定恶化，并减少 PH 细胞的兴奋性突触输入。社交隔离对 PH 细胞的影响，包括功能性谷氨酸能突触的减少和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸/N-甲基-D-天冬氨酸电荷量比的减少，仅在断奶后 2 周和 mPFC 中发生。我们得出结论，幼年时期的社交经历对 mPFC 中 5 层锥体神经元的特定亚型的功能发育起着至关重要的作用。由于这些神经元投射到皮质下结构，在关键期缺乏社交经验可能导致 mPFC 和皮质下靶区之间不成熟的神经回路。
