美国国立卫生研究院研究团队取得一项新突破。他们揭示了差异突触抑制介导脑深部刺激的治疗效果。相关论文于2025年10月16日发表于国际顶尖学术期刊《自然—神经科学》杂志上。

在这里，该课题组发现丘脑下核（STN）的高频DBS（帕金森病（PD）的常见靶点）激活传入轴突，同时抑制STN神经元。这些突触前和突触后的对比效应源于局部神经递质释放的减少，谷氨酸的减少比GABA的减少更大，将兴奋/抑制平衡转向抑制。STN神经元的化学发生抑制，而不是兴奋，模拟DBS对6-OHDA损伤PD小鼠的治疗效果。急性和慢性双侧化学发生STN抑制可恢复进展性PD模型的运动功能。这些发现表明，以谷氨酸能突触和GABA能突触的差异抑制为主导的STN抑制是治疗性DBS的关键机制。“化学发生DBS”，直接化学发生抑制突触后神经元，可能为PD和其他神经系统疾病提供一种侵入性更小、更实惠的电DBS替代方案。

据悉，深部脑刺激（DBS）有效治疗耐药神经和精神疾病，但其机制尚不清楚。

附：英文原文

Title: Differential synaptic depression mediates the therapeutic effect of deep brain stimulation

Author: Li, Jicheng, Zhou, Jingheng, He, Bo, Papaneri, Amy B., Kobzar, Nicholas P., Yeh, Alan C., Zhang, Ying, Cui, Guohong

Issue&Volume: 2025-10-16

Abstract: Deep brain stimulation (DBS) effectively treats drug-resistant neurological and psychiatric disorders, yet its mechanisms remain unclear. Here we show that high-frequency DBS of the subthalamic nucleus (STN), a common target for Parkinson’s disease (PD), activates afferent axons while inhibiting STN neurons. These contrasting presynaptic and postsynaptic effects arise from a decrease in local neurotransmitter release with a larger decrease in glutamate than GABA, shifting the excitation/inhibition balance toward inhibition. Chemogenetic inhibition, but not excitation, of STN neurons mimics the therapeutic effects of DBS in 6-OHDA-lesioned PD mice. Acute and chronic bilateral chemogenetic STN inhibition restores motor function in a progressive PD mouse model. These findings suggest that inhibition of STN, caused by differential depression of glutamatergic and GABAergic synapses, is a key mechanism of therapeutic DBS. ‘Chemogenetic DBS’, direct chemogenetic inhibition of postsynaptic neurons, may offer a less invasive and more affordable alternative to electrical DBS for PD and other neurological disorders.

DOI: 10.1038/s41593-025-02088-w

Source: https://www.nature.com/articles/s41593-025-02088-w