树突非线性对电场作用下神经编码的影响机制研究

Noninvasive electromagnetic brain modulation (hereinafter referred to as NBM) technique has been widely applied to probe cognitive functions and treat neuropsychiatric disorders. However, its application has outpaced our understanding of its mechanism. Exploring its action mechanism is of great significance to NBM device optimization and dose setting. The modulation of neural system with NBM-evoked electric field has obvious specificity, which is tightly related to the intrinsic properties of neuron, especially the dendritic nonlinearity. However, it is still unclear how dendritic nonlinearity influences neural coding stimulated by electric field. We hypothesize here that the nonlinearity of dendrite is able to control the integration of synaptic inputs, which directly participates in the initiation and output of action potentials in soma and further impacts neural coding. .This project characterizes the impacts of dendritic nonlinearity on its output as well as the relationship between dendritic output and neuronal response, to explain the mechanism underlying how dendritic nonlinearity participates in electric field-evoked neural coding. We use computational models to quantify dendritic gain, and then analyze how the nonlinearity of dendrite influences its output. By introducing electric field stimulus into the model, we describe the modulations of dendritic gain with electric field, and further determine how such field interacts with dendritic nonlinearity to result in dendritic output. After that, we use nonlinear dynamical method to investigate the connections that link dendritic output, action potential threshold and neuronal output gain, which is further used to uncover the biophysical mechanism of how dendritic output contributes to neuronal response.

无创式电磁脑调制（NBM）技术被广泛用于研究大脑的认知功能和神经精神疾病的治疗，但对其作用机制的理解远落后于应用，而机制研究对于NBM的装置优化和剂量设定具有重要意义。NBM诱发电场对神经活动的调节具有明显特异性，这与神经元固有特性密切相关，特别是树突非线性。然而，树突非线性如何影响电场作用下神经编码尚不清楚。项目提出假说：树突非线性通过调控树突对突触输入的运算结果，干预胞体动作电位的产生及发放进而影响神经编码。.项目描述树突非线性对树突输出的影响以及树突输出与神经响应的关系，阐释树突非线性参与电场诱发神经编码的机理。采用计算模型量化树突增益，分析树突非线性与树突输出的关系；建立电场作用下神经元模型，刻画电场对树突增益的调节规律，描述电场与树突非线性的相互作用及对树突输出的影响；采用非线性动力学方法，分析树突增益、放电阈值和神经元输出增益之间的关系，揭示树突输出影响神经响应的生物物理机制。

研究电场作用下神经元编码特性对于无创式脑调制技术的标准化和科学化具有重要意义。项目采用计算模型和动力学方法刻画电场作用下树突非线性运算特性和动作电位发放过程，有助于科学理解电场对神经编码的调节效应，为揭示无创式脑调制技术的作用机理提供了理论基础和科学依据。.根据NEURON中的“胞外机制”，建立了电场作用下不同形式神经元计算模型，用以描述树突形态、离子通道和放电起始动态。基于构建的计算模型，完成了如下三方面内容：.首先，研究了树突固有特性对树突非线性运算的调控规律。通过刻画树突直径、分支和突触输入位置与树突输出增益之间的关系，得到了树突形态对树突亚线性输出的影响规律。分析了树突Ca2+放电和Na+放电的动态特性，建立了二者与树突超线性输出之间的内在联系。通过计算树突ATP消耗，得到了突触强度、树突电压、胞体反传Na+放电和Ca2+通道抑制性对树突Ca2+放电的影响规律。.然后，研究了电场对树突非线性运算的调节规律。通过计算不同电场强度下树突的输出增益，得到了电场强度和空间形态对树突非线性运算的影响规律。通过计算树突Ca2+放电阈值，建立了电场参数与树突Ca2+放电的内在联系，得到了锥体神经元在电场作用下的重合检测特性。通过刻画树突能量消耗，得到了电场频率与树突响应之间的量化关系。.最后，分析了树突非线性对神经响应的影响机制。通过计算电场刺激阈值，得到了树突直径、长度、个数、弯曲和分支对电场作用下神经元响应的调控规律。采用相平面和分岔方法，揭示了树突Ca2+放电诱发胞体簇放电的动力学机制，建立了树突被动特性和动作电位阈值之间的生物物理联系。通过计算Na+放电能量消耗，得到了突触强度、兴奋抑制比、树突形态和主动电流对神经元输出的影响规律。通过计算胞体放电频率，建立了突触输入和电场参数与神经元逆向激活之间的内在联系。