Ma Kaihua, Gu Huaguang, Jia Yanbing
School of Aerospace Engineering and Applied Mechanics, Tongji University, Shanghai, 200092 China.
School of Mathematics and Statistics, Henan University of Science and Technology, Luoyang, 471000 China.
Cogn Neurodyn. 2024 Jun;18(3):1397-1416. doi: 10.1007/s11571-023-09960-0. Epub 2023 Apr 5.
A burst behavior observed in the lateral habenula (LHb) neuron related to major depressive disorder has attracted much attention. The burst is induced from silence by the excitatory -methyl-D-aspartate (NMDA) synapse or by the inhibitory stimulation, i.e., a post-inhibitory rebound (PIR) burst, which has not been explained clearly. In the present paper, the neuronal and synaptic dynamics for the PIR burst are acquired in a theoretical neuron model. At first, dynamic cooperations between the fast rise of inhibitory γ-aminobutyric acid (GABA) synapse, slow rise of NMDA synapse, and T-type calcium current to evoke the PIR burst are obtained. Similar to the inhibitory pulse stimulation, fast rising GABA current can reduce the membrane potential to a level low enough to de-inactivate the low threshold T-type calcium current to evoke a PIR spike, which can enhance the slow rising NMDA current activated at a time before or after the PIR spike. The NMDA current following the PIR spike exhibits slow decay to induce multiple spikes to form the PIR burst. Such results present a theoretical explanation and a candidate for the PIR burst in real LHb neurons. Then, the dynamical mechanism for the PIR spike mediated by the T-type calcium channel is obtained. At large conductance of T-type calcium channel, the resting state corresponds to a stable focus near Hopf bifurcation and exhibits an "uncommon" threshold curve with membrane potential much lower than the resting membrane potential. Inhibitory modulation induces membrane potential decreased to run across the threshold curve to evoke the PIR spike. At small conductance of the T-type calcium channel, a stable node appears and manifests a common threshold curve with higher membrane potential, resulting in non-PIR phenomenon. The results present the dynamic cooperations between neuronal dynamics and fast/slow dynamics of different synapses for the PIR burst observed in the LHb neuron, which is helpful for the modulations to major depressive disorder.
外侧缰核（LHb）神经元中观察到的与重度抑郁症相关的爆发行为引起了广泛关注。这种爆发由兴奋性N-甲基-D-天冬氨酸（NMDA）突触或抑制性刺激从静息状态诱发，即抑制后反弹（PIR）爆发，其机制尚未得到清晰解释。在本文中，通过理论神经元模型获得了PIR爆发的神经元和突触动力学。首先，得到了抑制性γ-氨基丁酸（GABA）突触的快速上升、NMDA突触的缓慢上升以及T型钙电流之间的动态协同作用，以诱发PIR爆发。与抑制性脉冲刺激类似，快速上升的GABA电流可将膜电位降低到足以使低阈值T型钙电流去失活的水平，从而诱发PIR尖峰，这可增强在PIR尖峰之前或之后某个时间激活的缓慢上升的NMDA电流。PIR尖峰后的NMDA电流表现出缓慢衰减，以诱发多个尖峰形成PIR爆发。这些结果为真实LHb神经元中的PIR爆发提供了理论解释和候选机制。然后，获得了由T型钙通道介导的PIR尖峰的动力学机制。在T型钙通道的大电导时，静息状态对应于霍普夫分岔附近的稳定焦点，并表现出一条“异常”的阈值曲线，其膜电位远低于静息膜电位。抑制性调制导致膜电位下降，穿过阈值曲线以诱发PIR尖峰。在T型钙通道的小电导时，出现一个稳定节点，并表现出具有较高膜电位的普通阈值曲线，导致非PIR现象。这些结果展示了LHb神经元中观察到的PIR爆发的神经元动力学与不同突触的快/慢动力学之间的动态协同作用，这有助于对重度抑郁症进行调制。
