3月22日，《公共科學圖書館—生物學》（PLoS Biology）發(fā)表了中科院上海生命科學研究院神經所舒友生研究組的最新成果：大腦皮層維持興奮和抑制動態(tài)平衡的新機制，即神經元的膜電位水平可以調控反饋抑制的強度。該工作由朱潔、江漫,、楊明坡和侯晗等合作完成。同期的PLoS Biology發(fā)表了題為“在皮層網(wǎng)絡中尋找平衡”（Finding Balance in Cortical Networks）的評論，對這項工作進行了專門介紹,。
大腦皮層各種功能的正常發(fā)揮依賴于皮層中興奮和抑制的動態(tài)平衡。在皮層神經網(wǎng)絡中，興奮性的錐體神經元和抑制性的中間神經元通過突觸結構形成局部神經環(huán)路,，這些環(huán)路是皮層中興奮-抑制平衡的結構基礎,。一般認為，興奮性神經元發(fā)放的動作電位（數(shù)碼信號）沿軸突傳導至突觸前膜,，通過突觸傳遞在抑制性神經元上產生興奮性突觸后電位（EPSP）,，如果達到特定的發(fā)放閾值，抑制性神經元會產生動作電位并在其支配的興奮性神經元上產生抑制性突觸后電位（IPSP）,，從而反饋抑制興奮性神經元,。大腦皮層的電活動狀態(tài)與行為息息相關，那么皮層又是如何在不同的電活動狀態(tài)下（即當神經元處于不同的膜電位水平時）維持興奮-抑制的動態(tài)平衡呢,？
朱潔等在離體腦薄片上應用膜片鉗技術同時記錄多個皮層神經元,，發(fā)現(xiàn)反饋性抑制受到突觸前錐體神經元膜電位的調控：錐體神經元的閾下膜電位去極化（興奮性提高）可增強其動作電位在突觸后錐體神經元上引起的雙突觸IPSP（抑制性增強）。進一步實驗證明,，雙突觸IPSP的增強是由抑制性中間神經元所介導：突觸前去極化增大動作電位在抑制性中間神經元上誘發(fā)EPSP（膜電位依賴的模擬信號）,，并使其發(fā)放動作電位的概率和數(shù)目增加，從而介導IPSP的增強,。這種膜電位依賴的EPSP和IPSP的變化由軸突D-電流（一種快激活但緩慢失活的鉀電流）所介導,。
太極圖顯示：大腦皮層中興奮性神經元（Excitatory）和抑制性神經元（Inhibitory）通過混和的數(shù)碼信號（101011……）和模擬信號（黃色曲線表示的膜電位依賴的調制信號）維持網(wǎng)絡中興奮和抑制的動態(tài)平衡。圖片由侯晗構思設計,。
該研究揭示了大腦皮層動態(tài)維持其網(wǎng)絡中興奮和抑制平衡的新機制,。由于皮層中這一平衡的破壞與癲癇、精神分裂癥等神經系統(tǒng)疾病有關,，這項研究成果可為相關疾病的臨床治療提供新思路,。
該研究得到了中國科學院、科技部,、國家自然科學基金委,、上海市科委等項目的資助。（生物谷Bioon.com）
生物谷推薦原文出處：
PLoS Biol 9(3): e1001032. doi:10.1371/journal.pbio.1001032
Membrane Potential-Dependent Modulation of Recurrent Inhibition in Rat Neocortex
Jie Zhu, Man Jiang, Mingpo Yang, Han Hou, Yousheng Shu*
Dynamic balance of excitation and inhibition is crucial for network stability and cortical processing, but it is unclear how this balance is achieved at different membrane potentials (Vm) of cortical neurons, as found during persistent activity or slow Vm oscillation. Here we report that a Vm-dependent modulation of recurrent inhibition between pyramidal cells (PCs) contributes to the excitation-inhibition balance. Whole-cell recording from paired layer-5 PCs in rat somatosensory cortical slices revealed that both the slow and the fast disynaptic IPSPs, presumably mediated by low-threshold spiking and fast spiking interneurons, respectively, were modulated by changes in presynaptic Vm. Somatic depolarization (>5 mV) of the presynaptic PC substantially increased the amplitude and shortened the onset latency of the slow disynaptic IPSPs in neighboring PCs, leading to a narrowed time window for EPSP integration. A similar increase in the amplitude of the fast disynaptic IPSPs in response to presynaptic depolarization was also observed. Further paired recording from PCs and interneurons revealed that PC depolarization increases EPSP amplitude and thus elevates interneuronal firing and inhibition of neighboring PCs, a reflection of the analog mode of excitatory synaptic transmission between PCs and interneurons. Together, these results revealed an immediate Vm-dependent modulation of cortical inhibition, a key strategy through which the cortex dynamically maintains the balance of excitation and inhibition at different states of cortical activity.
《PLoS生物學》發(fā)表文章（英文）
