Computer models of the electrical rhythmic activities in hippocampal neurons

(A)建立表现癫痫样事件(SLEs)的正常和病理状态下海马神经胶质网络电节律活动的宏观和微观计算机模型。(I)宏观水平模型通过耦合认知节律生成器(CRG)模型的群体来表征系统行为(我们的实验室团队以前报道过)。每个CRG由神经元模式的输入层(其传递函数由Volterra级数测量或从预定的设计函数中交替选择)组成，用于感知输入环境。神经元模式层的输出被前馈到WINFREE类型的环形装置，其变量通过静态非线性(代表波形)映射到可观测的输出变量。振铃装置的频率由神经元模式的输出进行调制，以提供对输入环境变化的“响应性适应”。耦合CRG被用来模拟病理状态，并被用作废除SLEs的神经调节策略的测试平台。(2)传统和“随机”Hodgkin-Huxley模型的微观模型，以描述锥体、中间神经元和神经胶质细胞的“细胞”模型中的离子传输机制。这些模型被用来研究(1)星形胶质细胞对超兴奋性的影响，以及(2)表征其状态的神经胶质网络电节律中的交频耦合机制。

(a) Develop macro and micro level computer models of the electrical rhythmic activity in hippocampal neuro-glial networks under normal and pathological states exhibiting seizure-like events (SLEs). (i) Macro level models characterize system behaviour by populations of coupled cognitive rhythm generator (CRG) models (previously reported by our lab team). Each CRG consists of an input layer of neuronal modes (whose transfer functions are measured from Volterra series or alternately chosen from predetermined design functions) for sensing the input environment. The outputs of the neuronal modes layer are feed-forward to a Winfree type ring device whose variables are mapped by a static nonlinearity (representing the wave shape) into an observable output variable. The frequencies of the ring device are modulated by the outputs of the neuronal modes to provide “responsive adaptation” to changes in the input environment. Coupled CRGs are utilized to model pathological states and are used as testing platforms of neuromodulation strategies for abolishment of SLEs. (ii) Micro level models of traditional and "stochastic" Hodgkin-Huxley type models to characterize ionic transport mechanisms in "cellular" models of pyramidal, interneuron and glial cells. These models are used to investigate (1) the effects of astrocytes on hyper-excitability, and (2) the mechanisms of cross frequency coupling in the electrical rhythms of the neuro-glial networks characterizing their states.