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昼夜节律和睡眠依赖性调节皮质中间神经元。

Circadian time- and sleep-dependent modulation of cortical parvalbumin-positive inhibitory neurons.

机构信息

Interdisciplinary Research Center on Biology and Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, Shanghai, China.

University of Chinese Academy of Sciences, Beijing, China.

出版信息

EMBO J. 2023 Feb 1;42(3):e111304. doi: 10.15252/embj.2022111304. Epub 2022 Dec 7.

Abstract

Parvalbumin-positive neurons (PVs) are the main class of inhibitory neurons in the mammalian central nervous system. By examining diurnal changes in synaptic and neuronal activity of PVs in the supragranular layer of the mouse primary visual cortex (V1), we found that both PV input and output are modulated in a time- and sleep-dependent manner throughout the 24-h day. We first show that PV-evoked inhibition is stronger by the end of the light cycle (ZT12) relative to the end of the dark cycle (ZT0), which is in line with the lower inhibitory input of PV neurons at ZT12 than at ZT0. Interestingly, PV inhibitory and excitatory synaptic transmission slowly oscillate in opposite directions during the light/dark cycle. Although excitatory synapses are predominantly regulated by experience, inhibitory synapses are regulated by sleep, via acetylcholine activating M1 receptors. Consistent with synaptic regulation of PVs, we further show in vivo that spontaneous PV activity displays daily rhythm mainly determined by visual experience, which negatively correlates with the activity cycle of surrounding pyramidal neurons and the dorsal lateral geniculate nucleus-evoked responses in V1. These findings underscore the physiological significance of PV's daily modulation.

摘要

钙结合蛋白阳性神经元(PVs)是哺乳动物中枢神经系统中主要的抑制性神经元。通过检测小鼠初级视觉皮层(V1)颗粒上层中 PV 神经元的突触和神经元活动的昼夜变化,我们发现,在整个 24 小时昼夜周期中,PV 的输入和输出都呈现时间依赖性和睡眠依赖性的调节方式。我们首先发现,相对于暗周期(ZT0)结束时,PV 诱导的抑制作用在光周期(ZT12)结束时更强,这与 ZT12 时 PV 神经元的抑制性输入低于 ZT0 时的情况一致。有趣的是,在光/暗周期中,PV 抑制性和兴奋性突触传递以相反的方向缓慢振荡。虽然兴奋性突触主要受经验调节,但抑制性突触受睡眠调节,通过乙酰胆碱激活 M1 受体来调节。与 PV 突触的调节一致,我们进一步在体内显示,自发的 PV 活动显示出主要由视觉经验决定的每日节律,其与周围锥体神经元的活动周期和 V1 中背外侧膝状体核诱发的反应呈负相关。这些发现强调了 PV 每日调节的生理意义。

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