Okamura Kazuya, Yoshino Hiroki, Ogawa Yoichi, Yamamuro Kazuhiko, Kimoto Sohei, Yamaguchi Yasunari, Nishihata Yosuke, Ikehara Minobu, Makinodan Manabu, Saito Yasuhiko, Kishimoto Toshifumi
Department of Psychiatry, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Mie Prefectural Mental Medical Center, Tsu, Mie 514-0818, Japan.
Cereb Cortex. 2023 Mar 21;33(7):3591-3606. doi: 10.1093/cercor/bhac294.
A lack of juvenile social experience causes various behavioral impairments and brain dysfunction, especially in the medial prefrontal cortex (mPFC). Our previous studies revealed that juvenile social isolation for 2 weeks immediately after weaning affects the synaptic inputs and intrinsic excitability of fast-spiking parvalbumin-expressing (FSPV) interneurons as well as a specific type of layer 5 (L5) pyramidal cells, which we termed prominent h-current (PH) cells, in the mPFC. However, since these changes were observed at the adult age of postnatal day 65 (P65), the primary cause of these changes to neurons immediately after juvenile social isolation (postnatal day 35) remains unknown. Here, we investigated the immediate effects of juvenile social isolation on the excitability and synaptic inputs of PH pyramidal cells and FSPV interneurons at P35 using whole-cell patch-clamp recording. We observed that excitatory inputs to FSPV interneurons increased immediately after juvenile social isolation. We also found that juvenile social isolation increases the firing reactivity of a subtype of FSPV interneurons, whereas only a fractional effect was detected in PH pyramidal cells. These findings suggest that juvenile social isolation primarily disturbs the developmental rebuilding of circuits involving FSPV interneurons and eventually affects the circuits involving PH pyramidal cells in adulthood.
缺乏青少年社交经验会导致各种行为障碍和大脑功能障碍,尤其是在内侧前额叶皮质(mPFC)。我们之前的研究表明,断奶后立即进行2周的青少年社会隔离会影响mPFC中快速放电的表达小白蛋白的(FSPV)中间神经元以及特定类型的第5层(L5)锥体细胞(我们称之为突出h电流(PH)细胞)的突触输入和内在兴奋性。然而,由于这些变化是在出生后第65天(P65)的成年期观察到的,青少年社会隔离后(出生后第35天)神经元这些变化的主要原因仍然未知。在这里,我们使用全细胞膜片钳记录研究了青少年社会隔离对P35时PH锥体细胞和FSPV中间神经元的兴奋性和突触输入的即时影响。我们观察到青少年社会隔离后,FSPV中间神经元的兴奋性输入立即增加。我们还发现,青少年社会隔离增加了FSPV中间神经元亚型的放电反应性,而在PH锥体细胞中仅检测到部分影响。这些发现表明,青少年社会隔离主要扰乱了涉及FSPV中间神经元的回路的发育重建,并最终影响成年期涉及PH锥体细胞的回路。