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

Zongyi Xu, Wei Duan, Shuyu Yuan, Xiaoxue Zhang, Chong You, Jin-Tai Yu, Jian Wang, Jia-Da Li, Suixin Deng () and Yousheng Shu ()
Additional contact information
Zongyi Xu: Fudan University
Wei Duan: Fudan University
Shuyu Yuan: Fudan University
Xiaoxue Zhang: Fudan University
Chong You: Fudan University
Jin-Tai Yu: Fudan University
Jian Wang: Fudan University
Jia-Da Li: Central South University
Suixin Deng: Central South University
Yousheng Shu: Fudan University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract 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.

Date: 2025
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-59113-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-59113-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-59113-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().