Perineuronal nets (PNNs) surrounding fast-spiking, parvalbumin (PV) inhibitory interneurons are vital for providing excitatory:inhibitory balance within cortical circuits, and this balance is impaired in disorders such as schizophrenia, autism spectrum disorder, and substance use disorders. These disorders are also associated with altered diurnal rhythms, yet few studies have examined the diurnal rhythms of PNNs or PV cells. We measured the intensity and number of PV cells and PNNs labeled with Wisteria floribunda agglutinin (WFA) in the rat prelimbic medial prefrontal cortex (mPFC) at Zeitgeber times (ZT) ZT0, 6, 12, and 18. We also measured the oxidative stress marker 8-oxo-deoxyguanosine (8-oxo-dG). Relative to ZT0, the intensities of PNN and PV staining were increased in the dark (active) phase compared with the light (inactive) phase. The intensity of 8-oxo-dG was decreased from ZT0 at all time points (ZT6,12,18), in both PV cells and non-PV cells. To examine corresponding changes in inhibitory and excitatory inputs, we measured GAD 65/67 and vGlut1 puncta apposed to PV cells with and without PNNs. Relative to ZT6, there were more excitatory puncta on PV cells surrounded by PNNs at ZT18, but no changes in PV cells devoid of PNNs. No changes in inhibitory puncta were observed. Whole-cell slice recordings in fast-spiking (PV) cells with PNNs showed an increased ratio of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor:N-methyl-D-aspartate receptor (AMPA:NMDA) at ZT18 vs. ZT6. The number of PV cells and co-labeled PV/PNN cells containing the transcription factor orthodenticle homeobox 2 (OTX2), which maintains PNNs, showed a strong trend toward an increase from ZT6 to ZT18. These diurnal fluctuations in PNNs and PV cells are expected to alter cortical excitatory:inhibitory balance and provide new insights into treatment approaches for diseases impacted by imbalances in sleep and circadian rhythms.

中文翻译：

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大鼠前额内侧皮层神经周围神经网和小白蛋白神经元的昼夜变化

围绕快速加标，小白蛋白（PV）抑制的中间神经元的神经周围神经网络（PNN）对于在皮质回路内提供兴奋性：抑制性平衡至关重要，并且这种平衡在诸如精神分裂症，自闭症谱系障碍和物质使用障碍等疾病中受损。这些疾病也与昼夜节律的改变有关，但是很少有研究检查PNN或PV细胞的昼夜节律。我们测量了Zeitgeber时间（ZT）ZT0、6、12和18时大鼠前肢内侧前额叶皮层（mPFC）中标有紫藤的紫藤凝集素（WFA）标记的PV细胞和PNN的强度和数量。我们还测量了氧化应激标记8-氧代-脱氧鸟苷（8-氧代-dG）。相对于ZT0，在黑暗（活动）阶段与轻（非活动）阶段相比，PNN和PV染色的强度增加。在所有时间点（ZT6、12、18），PV电池和非PV电池中的8-oxo-dG强度均从ZT0降低。为了检查抑制性和兴奋性输入的相应变化，我们测量了GAD 65/67和vGlut1点状点与有和没有PNN的PV电池的相对位置。相对于ZT6，在ZT18处被PNN包围的PV细胞上有更多的兴奋点，但缺少PNN的PV细胞没有变化。没有观察到抑制性泪点的变化。带有PNN的快速加标（PV）细胞中的全细胞切片记录显示，α-氨基-3-羟基-5-羟基-5-甲基-4-异恶唑丙酸受体：N-甲基-D-天冬氨酸受体（AMPA：NMDA）的比例增加）在ZT18与ZT6之间进行比较。包含转录因子直齿同源盒2（OTX2）并保持PNN的PV细胞和共标记的PV / PNN细胞的数量，从ZT6上升到ZT18的趋势很明显。预计PNN和PV细胞的这些昼夜波动会改变皮层的兴奋性：抑制性平衡，并为受睡眠和昼夜节律不平衡影响的疾病的治疗方法提供新见解。