超极化激活阳离子流(Ih流)调控海马Theta节律的动力学机制

The Theta (4~12 Hz) rhythms of the hippocampus in the brain are low-frequency oscillations formed by synchronous activity of a large number of neurons and are associated with the brain functions such as spatial cognition, memory formation, and sensorimotor integration. The formation of Theta (4~12 Hz) rhythms is related to the inhibitory synapses and hyperpolarization-activated cation current (Ih). Although Ih current exists in many types of neurons in the hippocampus, the dynamical mechanism underlying the role of Ih current in the formation of Theta rhythms has received little attention. In this project, we will focus on the dynamical characteristics of Ih current, take how inhibitory postsynaptic currents (hyperpolarization current) activate Ih current as the breakthrough point, and consider the network structure and noise to study the dynamical mechanisms of the hippocampal Theta rhythms through model simulation and analysis. The research project includes: to analyze the effect of Ih current on the characteristics of neuronal electronic activity using dynamical methods; to investigate the effect of Ih current, synapses (excitatory and inhibitory) and their interactions associated with the formation of Theta rhythms in the isolated hippocampus (neuronal networks composed of neurons within hippocampus) and septo-hippocampal reciprocal loop (neuronal networks composed of neurons within both medial septum and hippocampus); to study the capacity of Ih current on keeping synchronization degree and frequency range of the Theta rhythms in the two types of neuronal networks with noise disturbance. This research project will reveal the specific effects of Ih current on the development of synchronization in the neuronal networks and so provide theoretical basis for deeper insight into hippocampal theta rhythms, which have important significance in both nonlinear dynamics and biology.

脑内海马的Theta节律(4~12Hz)是大量神经元同步活动形成的低频振荡，影响大脑的空间认知和记忆形成等功能，其产生与抑制性突触和超极化激活阳离子流(Ih)有关。海马内多种神经元具有Ih流，但其在Theta节律动力学机制中的作用很少被关注。本研究将通过理论模型，以Ih流的动力学特征为核心，以抑制性突触电流(即超极化电流)如何激活Ih流为突破点，并考虑网络结构和噪声等因素，综合研究Theta节律形成的动力学机制。内容包括：利用动力学方法分析Ih流对神经元电活动特性的影响；揭示Ih流和突触(包括兴奋和抑制)及两者的相互作用在海马自身网络、内侧隔阂-海马网络中Theta节律形成的机制；研究Ih流在实际环境(噪声等因素)中对两类网络的同步和Theta频率范围维持能力的影响。本研究将揭示Ih流在网络同步振荡形成中的特殊作用，为认识海马Theta节律产生提供理论帮助，具有重要的动力学和生物学意义。

项目通过对神经动力系统的数值计算和理论分析，进行了以下工作：首先，揭示了超极化激活电流（Ih流）引起阈下theta振荡共振的动力学机制。针对实验发现Ih流对海马神经元阈下振荡共振的产生起着决定性作用的认识，通过构建簇放电神经元模型，仿真了阈下共振现象，并借助于动力学中的稳定性和分岔理论，揭示阈下振荡产生的原因。该结果从动力学理论的角度，给出了阈下振荡产生的机制，为深入研究Ih流调控theta振荡节律产生提供了基础。其次，基于实验和模型研究分别发现Ih流有助于抑制后反跳放电现象和Hopf分岔的产生，揭示了抑制性自突触和兴奋性自突触对神经元放电频率调控具有反常作用的机制。根据数值计算获得的神经元动作电位阈值曲线的非线性特点，发现并解释了抑制后反跳放电现象和抑制性自突触诱发的从静息/阶段放电到连续快速放电转变的反常非线性现象产生的原因；借助于Hopf分岔点附近动力学行为的特点，发现并解释了兴奋性自突触可将高频的快速放电转变为低频的混合振荡放电的非线性反常现象，并与抑制性自突触诱发引起的低频放电进行了比较。该结果扩展了神经系统中的反常非线性现象，给出了突触和Ih流相互作用引起神经元theta节律低频放电的可能情况，拓展了对Ih流在神经系统中独特作用的认识。最后，对抑制性和兴奋性耦合神经元的同步振荡活动进行了研究，给出了兴奋性和抑制性突触诱发稳定同步振荡的条件。分别构建了抑制性和兴奋性耦合神经元，采用动力学中的对称理论、稳定性切换和分岔理论，分别给出了抑制性和兴奋性耦合神经元同步振荡的条件。该结果从理论上给出了兴奋性和抑制性神经网络同步振荡的不同，为进一步深入理解海马神经元网络形成稳定的同步振荡活动提供认识。