Objective: This study aimed to identify the specific STN cell type and circuit responsible for alleviating parkinsonian motor symptoms through targeted neural modulation.
Background: The subthalamic nucleus (STN) is a key target for deep brain stimulation (DBS) in Parkinson’s disease. However, the specific STN subpopulations responsible for alleviating parkinsonian motor symptoms remain unclear. Therefore, identifying the precise neural circuits involved in motor symptom improvement with STN-DBS is crucial.
Method: We targeted parvalbumin (PV) neurons within the STN using a PV-Cre transgenic mouse model. Parkinsonian mouse models (unilateral 6-OHDA and DAT-PARIS-PV genetic models) were evaluated with the pole test for motor function. Optogenetic stimulation was applied using Channelrhodopsin (ChR2, 100 Hz, 5 ms pulse width, 5 mW/mm²) unilaterally (6-OHDA model) and bilaterally (DAT-PARIS model). We designed viral vectors for Cre-dependent (Jx-on) and non-Cre-dependent (Jx-off) ChR2 expression to selectively target PV-STN and non-PV-STN populations. For chemogenetic inhibition, we used FlexON-hM4Di and FlexOFF-hM4Di for PV-STN and non-PV-STN modulation, respectively. Finally, we conducted the apomorphine rotation test with unilateral optogenetic stimulation in the 6-OHDA model (PV and non-PV) to test the effect of PV modulation.
Results: In the pole test, activation of PV-STN neurons improved motor symptoms in both Parkinsonian models, whereas stimulation of non-PV STN neurons had no significant effect. Similarly, chemogenetic inhibition of PV-STN neurons produced a significant effect, while inhibition of non-PV STN neurons did not. Additionally, in the apomorphine rotation test with optogenetic stimulation in the unilateral 6-OHDA model, activation of PV-STN neurons led to cessation of rotation, whicn was not observed with non-PV STN inhibition.
Conclusion: Cell-type specific bidirectional modulation of STN neurons rescue Parkinsonian Bidirectional modulation of the parvalbumin-positive subthalamic subpopulation improved motor symptoms in the Parkinsonian mouse model. These findings may contribute to the development of next-generation, cell type- and circuit-specific STN-DBS for Parkinson’s disease.motor symptom.
To cite this abstract in AMA style:
JH. Shin, HK. Chung, JH. Kim, JS. Yook, J. Kim, B. Jeon. Cell-type specific bidirectional modulation of STN neurons rescue Parkinsonian motor symptom. [abstract]. Mov Disord. 2025; 40 (suppl 1). https://www.mdsabstracts.org/abstract/cell-type-specific-bidirectional-modulation-of-stn-neurons-rescue-parkinsonian-motor-symptom/. Accessed October 5, 2025.« Back to 2025 International Congress
MDS Abstracts - https://www.mdsabstracts.org/abstract/cell-type-specific-bidirectional-modulation-of-stn-neurons-rescue-parkinsonian-motor-symptom/