3月22日，《公共科学图书馆—生物学》（PLoS Biology）发表了中科院上海生命科学研究院神经所舒友生研究组的最新成果：大脑皮层维持兴奋和抑制动态平衡的新机制，即神经元的膜电位水平可以调控反馈抑制的强度。该工作由朱洁、江漫、杨明坡和侯晗等合作完成。同期的PLoS Biology发表了题为“在皮层网络中寻找平衡”（Finding Balance in Cortical Networks）的评论，对这项工作进行了专门介绍。
大脑皮层各种功能的正常发挥依赖于皮层中兴奋和抑制的动态平衡。在皮层神经网络中，兴奋性的锥体神经元和抑制性的中间神经元通过突触结构形成局部神经环路，这些环路是皮层中兴奋-抑制平衡的结构基础。一般认为，兴奋性神经元发放的动作电位（数码信号）沿轴突传导至突触前膜，通过突触传递在抑制性神经元上产生兴奋性突触后电位（EPSP），如果达到特定的发放阈值，抑制性神经元会产生动作电位并在其支配的兴奋性神经元上产生抑制性突触后电位（IPSP），从而反馈抑制兴奋性神经元。大脑皮层的电活动状态与行为息息相关，那么皮层又是如何在不同的电活动状态下（即当神经元处于不同的膜电位水平时）维持兴奋-抑制的动态平衡呢？
朱洁等在离体脑薄片上应用膜片钳技术同时记录多个皮层神经元，发现反馈性抑制受到突触前锥体神经元膜电位的调控：锥体神经元的阈下膜电位去极化（兴奋性提高）可增强其动作电位在突触后锥体神经元上引起的双突触IPSP（抑制性增强）。进一步实验证明，双突触IPSP的增强是由抑制性中间神经元所介导：突触前去极化增大动作电位在抑制性中间神经元上诱发EPSP（膜电位依赖的模拟信号），并使其发放动作电位的概率和数目增加，从而介导IPSP的增强。这种膜电位依赖的EPSP和IPSP的变化由轴突D-电流（一种快激活但缓慢失活的钾电流）所介导。
太极图显示：大脑皮层中兴奋性神经元（Excitatory）和抑制性神经元（Inhibitory）通过混和的数码信号（101011……）和模拟信号（黄色曲线表示的膜电位依赖的调制信号）维持网络中兴奋和抑制的动态平衡。图片由侯晗构思设计。
该研究揭示了大脑皮层动态维持其网络中兴奋和抑制平衡的新机制。由于皮层中这一平衡的破坏与癫痫、精神分裂症等神经系统疾病有关，这项研究成果可为相关疾病的临床治疗提供新思路。
该研究得到了中国科学院、科技部、国家自然科学基金委、上海市科委等项目的资助。（生物谷Bioon.com）
生物谷推荐原文出处：
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生物学》发表文章（英文）
