Scholarlink

<p>High-frequency deep brain stimulation (DBS) at subthalamic nucleus (STN) is an effective therapy for Parkinson’s disease (PD), but the underlying mechanisms remain unclear. Here we find an important role of asynchronous release (AR) of GABA induced by high-frequency stimulation (HFS) in alleviating motor functions of dopamine-depleted male mice. Electrophysiological recordings reveal that 130-Hz HFS causes an initial inhibition followed by desynchronization of STN neurons, largely attributable to presynaptic GABA release. Low-frequency stimulation at 20 Hz, however, produces much weaker AR and negligible effects on neuronal firing. Further optogenetic and cell-ablation experiments demonstrate that activation of parvalbumin axons, but not non-parvalbumin axons, from external globus pallidus (GPe) is both necessary and sufficient for DBS effects. Reducing AR diminishes the high-frequency DBS effect, while increasing AR allows low-frequency DBS to achieve a therapeutic benefit. Therefore, asynchronous GABA release from GPe PV neurons may contribute significantly to the therapeutic effects of high-frequency DBS.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Deep brain stimulation alleviates Parkinsonian motor deficits through desynchronizing GABA release in mice

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年4月19日

查看全文
  • Zongyi Xu,
  • Wei Duan,
  • Shuyu Yuan,
  • Xiaoxue Zhang,
  • Chong You,
  • Jin-Tai Yu,
  • Jian Wang,
  • Jia-Da Li,
  • Suixin Deng,
  • Yousheng Shu

摘要

High-frequency deep brain stimulation (DBS) at subthalamic nucleus (STN) is an effective therapy for Parkinson’s disease (PD), but the underlying mechanisms remain unclear. Here we find an important role of asynchronous release (AR) of GABA induced by high-frequency stimulation (HFS) in alleviating motor functions of dopamine-depleted male mice. Electrophysiological recordings reveal that 130-Hz HFS causes an initial inhibition followed by desynchronization of STN neurons, largely attributable to presynaptic GABA release. Low-frequency stimulation at 20 Hz, however, produces much weaker AR and negligible effects on neuronal firing. Further optogenetic and cell-ablation experiments demonstrate that activation of parvalbumin axons, but not non-parvalbumin axons, from external globus pallidus (GPe) is both necessary and sufficient for DBS effects. Reducing AR diminishes the high-frequency DBS effect, while increasing AR allows low-frequency DBS to achieve a therapeutic benefit. Therefore, asynchronous GABA release from GPe PV neurons may contribute significantly to the therapeutic effects of high-frequency DBS.