Hua Hongtao, Gu Huaguang, Ma Kaihua, Jia Yanbing, Wu Liang
School of Mathematics and Science, Henan Institute of Science and Technology, Xinxiang, 453003, China.
School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai, 200092, China.
Sci Rep. 2025 Mar 14;15(1):8886. doi: 10.1038/s41598-025-92647-9.
Enhanced activity of inhibitory neurons, which is often used to suppress behaviors of pyramidal neurons to treat brain diseases, whereas can enhance spiking to a mixed-mode bursting (MMB) in recent experiments on migraine and seizure. The MMB contains a phase with high level of membrane potential/extracellular potassium concentration ([K]), which can propagate to form spreading depolarization (SD) wave. Different from the common view that the MMB/SD is often induced by enhanced positive effect or [K], in the present paper, dynamics and conditions for the uncommon MMB/SD evoked by enhanced inhibitory synaptic current are obtained in a theoretical model. Firstly, in addition to the well-known positive threshold across which the common MMB is induced by positive effect, a spiking pyramidal neuron exhibits a novel negative threshold with a low level of [K] for the MMB. A long and strong inhibitory stimulation suppresses the spiking to silence phase via a saddle-node bifurcation on an invariant circle at first and then run across the negative threshold, triggering positive feedback to enhance membrane potential and [K] to levels high enough, then resulting in the uncommon MMB. Secondly, in a coupling model, enhanced inhibitory effect for enhanced spiking activity of interneuron and conductance of inhibitory synapse, and enhanced spiking activity of pyramidal neuron, are favorable for the uncommon MMB. Then, reducing these activities or parameters present potential measures to prevent the MMB. Finally, in network model, the uncommon MMB of a pyramidal neuron can induce SD wave. The results present a novel theoretical explanation to the uncommon MMB/SD, counterintuitive function of the inhibitory interneuron, and potential measures to treat the diseases.
抑制性神经元活动增强常用于抑制锥体神经元的行为以治疗脑部疾病，然而在近期关于偏头痛和癫痫的实验中，这种增强却能使放电增强并转变为混合模式爆发（MMB）。MMB包含一个膜电位/细胞外钾离子浓度（[K]）较高的阶段，该阶段可传播形成扩散性去极化（SD）波。与通常认为MMB/SD常由增强的正向作用或[K]诱导的观点不同，本文在一个理论模型中得到了由增强的抑制性突触电流诱发的罕见MMB/SD的动力学和条件。首先，除了众所周知的由正向作用诱导常见MMB的正阈值外，一个放电的锥体神经元对于MMB还表现出一个在[K]水平较低时的新负阈值。长时间且强烈的抑制性刺激首先通过不变圆上的鞍结分岔将放电抑制到静息阶段，然后越过负阈值，触发正反馈以将膜电位和[K]增强到足够高的水平，进而导致罕见的MMB。其次，在一个耦合模型中，增强中间神经元的放电活动和抑制性突触的电导的抑制作用增强，以及锥体神经元的放电活动增强，都有利于罕见的MMB。然后，降低这些活动或参数是预防MMB的潜在措施。最后，在网络模型中，一个锥体神经元的罕见MMB可诱导SD波。这些结果为罕见的MMB/SD、抑制性中间神经元的反直觉功能以及治疗疾病的潜在措施提供了一种新的理论解释。
