大脑皮层是由各种神经元组成的复杂但有序的超级神经网络，是脑高级认知功能的结构基础。皮层网络中兴奋性和抑制性信号的动态平衡是正常脑电活动发生和脑功能发挥的前提，但是网络动态平衡的机制尚不清楚。我们之前的研究揭示了皮层锥体细胞的兴奋性决定机制，抑制性递质GABA的非同步化释放模式，以及交互抑制微环路受膜电位调节现象。本项目基于这些前期工作，拟多角度研究皮层网络中兴奋和抑制的动态平衡机制，包括：1）在细胞水平，探讨谷氨酸能神经元和GABA能神经元的兴奋性决定机制；2）在突触水平，研究同步化和非同步化递质释放在网络平衡中的作用；3）在微环路水平，探讨交互抑制微环路的突触连接特点及其工作模式；4）在网络水平，研究神经调质对网络平衡和脑活动状态（Brain state）的调节及其机制。这项研究将使我们对大脑皮层的功能基础及相关脑疾病的发病机理有更深入的认识，为干预皮层异常网络活动提供线索和理论依据。

The cerebral cortex, which consists of different types of neurons, is a complex but well-organized super neural network, forming the structural basis for brain cognitive functions. Previous studies showed that the dynamic maintenance of excitation-inhibition (E-I) balance is critical for the generation of normal brain activities and the execution of brain functions, the underlying mechanism, however, remains unclear. Our previous findings revealed the mechanism for action potential initiation (i.e. excitability) and backpropagation in cortical pyramidal neurons, the mode of asynchronous GABA release from inhibitory cortical interneurons, and the membrane potential-dependent modulation of recurrent inhibition in microcircuits. In this project, we seek to further investigate the mechanisms for the dynamic E-I balance in the cortex. Specific aims include: 1) at cellular level, investigating the mechanisms for action potential initiation in both glutamatergic and GABAergic neurons; 2) at synapse level, determining the contribution of both synchronous and asynchronous transmitter release to the E-I balance in cortical network; 3) at microcircuit level, determining the synaptic connection and operation strategy of microcircuits that mediate recurrent inhibition; 4) at network level, investigating the role of neuromodulators in regulating the E-I balance and brain states. This study will provide profound insights into the neural substrates of cortical functions and pathogenesis of related brain disorders, and offer clues for intervening abnormal cortical activities.