视皮层神经元网络时空行为的动力学机制研究

Synchronous oscillation were observed in the experiments on visual cortex with external visual stmulus, and spiral waves were discovered in recent experiments with inhibatory middle neurons blocked and M-type potassium current of neurons blocked. Modifications of M-type potassium current can induce the transition between different　types of bifucations in single neurons. In this project, dynamics of the spatio-temporal behaviors in the visual cortex are studied, by the combination between biological experiments and numerical simulation of theoretical models. Primary visual cortex slices are usded as experimental model. The transition between different types of bifurcations in single pyramidal neurons induced by modification of M-type current are recored by patch clamp, and spatio-temporal behaviors of the brain slice are recored by volyage-sensitive dyes before and after modification of M-type current, block of middle neurons and application of external stimulus throug a stimulor. Based on the biological reality, neuronal network that can describe visual cortex are set up. The influences of transition between different types of bifurcations of pyramidal neruons, inhibatiory middle neurons, extrnal stimulus and stochastic factors on the spatio-temporal behaviors are studied. Combining the experimental and theoretical results, the roles of single neuronal's dynamics and modification factors in the emergency of the spiral waves and synchronous behaviors in the network, and the unified understanding of the siral waves and synchronous behaviors are identified. The results are helpful to further study the spatio-temporal bahviors and physiological functions of visual cortex, and the dynamcis of neuronal networks.

生物学实验发现,外界视觉刺激下的大脑视皮层能产生同步振荡；近期则发现在阻断抑制性中间神经元和阻断神经元的M型钾电流时更易产生螺旋波；而有实验提示改变M型钾电流可以引起神经元电活动的分岔类型的改变。本项目拟通过模型理论仿真结合生物学实验来阐释视皮层网络时空行为的动力学机制。实验选用视皮层脑片，通过膜片钳技术确认改变M型钾电流确实可以引起的锥体神经元分岔类型的转迁；通过电压敏感染料来记录抑制性中间神经元被阻断前后、改变M型钾电流前后、通过刺激器施加外界刺激前后脑片的时空行为。依据生物学实际搭建网络模型，研究锥体神经元的分岔类型、抑制性中间神经元、外界刺激和随机因素对网络时空行为的影响。综合实验和理论模型结果，分析单元振子特性以及调控因素对螺旋波和时空行为的同步程度的影响，统一认识螺旋波和同步振荡等时空行为。该结果有助于促进对视皮层的时空行为和生理功能以及网络时空动力学的深入研究。

通过理论模型结合实验，揭示了视皮层网络的时空模式转迁以及对网络内单神经元动力学行为、神经元类型、突触类型和网络结构的依赖，内容包括：增加神经元网络内I型神经元的比例，时空模式发生转迁，出现去同步化并最终产生螺旋波；降低网络内抑制神经元的比例，神经元网络时空模式发生转迁，出现去同步过程，并最终出现螺旋波；稀疏化网络结构会不利于螺旋波的生成；进一步，利用快慢变量分离“解剖”单神经元的动力学特点，揭示了在不同相位具有不同的动力学响应；利用这一动力学响应，结合耦合电流的时变特征，从理论上解释多类复杂的时空动力学行为的产生机制，包括同步和去同步行为；也为利用单元动力学解释网络复杂时空动力学行为提供了科研示例和具体的方法和流程；利用视皮层切片进行实验，通过施加药物影响M电流改变神经元从II型变为I型、阻断抑制性中间神经元验证了理论模型的时空模式转迁和螺旋波的结果。通过新的数据分析手段，获得了精神分裂症的包括视皮层在内的脑网络的样本熵等非线性动力学特征的变化。综合理论和实验模型结果，认识单元振子特性、不同类单元的协同以及网络结构等对螺旋波和同步行为的影响，统一认识了螺旋波和同步振荡是时空行为转迁过程的不同模式。研究结果有助于认识视皮层的时空行为转迁特别是螺旋波的生成，对于调控螺旋波及其对应的疾病癫痫和认识精神分裂症有重要的理论指导意义。