经颅磁声电刺激强度对小鼠前额叶皮质网络可塑性的影响

Effect of transcranial magneto-acousto-electrical stimulation on the plasticity of the prefrontal cortex network in mice

背景:经颅磁声电刺激是一种新型无创的神经调控技术,利用超声波与静磁场耦合作用产生的感应电场调节神经系统的放电活动,但其影响大脑突触可塑性的作用机制研究尚浅。目的:探讨经颅磁声电刺激强度对小鼠前额叶皮质神经网络突触可塑性的影响。方法:①动物实验:将24只C57小鼠平均且随机分为4组,对照组(接受伪刺激)、刺激6.35 W/cm^(2)组(接受0.3 T、6.35 W/cm^(2)的耦合刺激)、刺激17.36 W/cm^(2)组(接受0.3 T、17.36 W/cm^(2)组的耦合刺激)和刺激56.25 W/cm^(2)组(接受0.3 T、56.25 W/cm2的耦合刺激),记录小鼠执行T迷宫过程中局部场电位信号和行为学正确率。②建模仿真实验:构建经颅磁声电刺激小鼠前额叶皮质神经网络模型,分别比较不同刺激强度下神经网络结构连接特性。结果与结论:①经颅磁声电刺激能够有效缩短小鼠行为学习时间,工作记忆能力得到改善(P<0.05),且习得行为后继续刺激小鼠前额叶,各组小鼠T迷宫行为学实验准确度没有明显差异(P>0.1)。分析小鼠前额叶局部场电位信号发现经颅磁声电刺激促进了β节律与γ节律能量增强;而随刺激强度升高,β节律与γ节律出现了非同步性下降;通过β-γ相位幅值耦合发现,刺激增强了神经网络适应新的信息和任务要求的能力变化。②建模仿真发现,刺激使得神经网络放电水平增强,长时程突触权重水平提高而短时程突触权重仅在刺激强度较高时降低。③研究结果表明,不同的刺激强度与神经网络功能结构的影响存在复杂的非线性关系;这种神经调控技术为治疗突触功能障碍和神经网络异常等相关神经疾病方面提供新的可能。

BACKGROUND:Transcranial magneto-acoustic-electrical stimulation is a novel non-invasive neural regulation technique that utilizes the induced electric field generated by the coupling effect of ultrasound and static magnetic field to regulate the discharge activity of the nervous system.However,the mechanism by which it affects synaptic plasticity in the brain is still not enough.OBJECTIVE:To explore the effect of transcranial magneto-acoustic-electrical stimulation intensity on synaptic plasticity of the prefrontal cortex neural network in mice.METHODS:(1)Animal experiment:Twenty-four C57 mice were equally and randomly divided into four groups:the control group receiving pseudo-stimulation,the 6.35 W/cm^(2) stimulation group receiving coupled stimulation of 0.3 T,6.35 W/cm^(2),the 17.36 W/cm^(2) stimulation group receiving coupled stimulation of 0.3 T,17.36 W/cm^(2),and the 56.25 W/cm^(2) stimulation group receiving coupled stimulation of 0.3 T,56.25 W/cm^(2).The local field potential signals and behavioral correctness were recorded during the execution of T-maze in mice.(2)Modeling and simulation experiments:A neural network model of the prefrontal cortex in mice stimulated by transcranial magneto-acoustic-electrical stimulation was constructed to compare the structural connectivity characteristics of the neural network under different stimulation intensities.RESULTS AND CONCLUSION:Transcranial magneto-acoustic-electrical stimulation could effectively shorten the behavior learning time,improve the working memory ability of mice(P<0.05),and continue to stimulate the frontal lobe of mice after learning behavior.There was no significant difference in the accuracy of the T-maze behavioral experiment among the experimental groups(P>0.1).Analysis of local field potential signals in the frontal lobe of mice revealed that transcranial magneto-acoustic-electrical stimulation promoted energy enhancement of β andγrhythms.As the stimulation intensity increased,there was an asynchronous decrease in β andγrhythms.Through β-γphase amplitude coupling,it was found that stimuli could enhance the neural network’s ability to adapt to new information and task requirements.Modeling and simulation experiments found that stimulation could enhance the discharge level of the neural network,increase the long-term synaptic weight level,and decrease the short-term synaptic weight level only when the stimulation intensity was high.To conclude,there is a complex nonlinear relationship between different stimulus intensities and the functional structure of neural networks.This neural regulation technique may provide new possibilities for the treatment of related neurological diseases such as synaptic dysfunction and neural network abnormalities.