探究PV+抑制性神经元功能受睡眠/觉醒周期调控的方式、机制与生理意义

我们已发表的工作首次发现皮层锥体神经元的兴奋/抑制平衡在昼夜周期中发生大幅度振荡，依赖于睡眠调控的抑制性神经输入是振荡发生的主要因素。表达PV的抑制性神经元在皮层中数量最多，是锥体神经元抑制性输入的主要来源。因此，我们推测PV神经元的功能在昼夜间被睡眠/觉醒周期紧密调控。我们的初步研究结果显示PV神经元的突触传递及自发神经活动在昼夜间确实发生显著变化。在该项目中，我们将综合运用电生理、光遗传、在体钙成像、行为操控等手段，首先夯实PV神经元功能昼夜间被节律性调控这一全新发现，再深入探究调控的具体机制并阐明其生理意义。目前大量研究都表明PV神经元的功能直接影响脑认知能力，其功能失调与许多脑疾病关系密切。深入阐析睡眠/觉醒周期对PV神经元功能的天然调控作用与机制对我们认识脑功能的自然维持与调控，了解与PV神经元功能异常相关的脑疾病发病机制，促进我们对睡眠的生理功能的认识都有重要意义。

We previously show that the E/I balance of cortical pyramidal neuron is tightly modulated during the light/dark cycle. This is mainly caused by a dynamic and sleep-dependent fluctuation of inhibition. Parvalbumin (PV)+ inhibitory neurons are the most abundant GABAergic interneurons in cortex. They form strong synaptic connections with the surrounding pyramidal neurons. Therefore, we speculate that the function of PV+ neuron is also dynamically modulated by the natural sleep/wake cycle. This hypothesis is supported by our preliminary results showing that both synaptic transmission and spontaneous neural activity of PV+ neuron are rhythmically altered during the 24h day. We propose to further investigate the functional modulation of PV+ neuron by the sleep/wake cycle and its underlying mechanism by applying interdisciplinary methods including electrophysiology, optogenetic, in vivo Ca2+ imaging, behavioral manipulation, et al.,. Many studies have already shown that PV+ neuron plays critical role in brain function. Dysregulation of PV+ neuron is tightly associated with many brain diseases. Hence, our study will provide important information and new insight on PV+ neuron regulation and its associated brain function and diseases. In addition, by understanding how sleep and sleep/wake regulates PV+ neuron, it will expand our knowledge about the critical role of sleep.