Integrating artificial intelligence and optogenetics for Parkinson’s disease diagnosis and therapeutics in male mice

Bobae Hyeon, Jaehyun Shin, Jae-Hun Lee, Woori Kim, Jea Kwon, Heeyoung Lee, Dae-gun Kim, Choong Yeon Kim, Sian Choi, Jae-Woong Jeong, Kwang-Soo Kim, C. Justin Lee (), Daesoo Kim () and Won Do Heo ()
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Bobae Hyeon: Korea Advanced Institute of Science and Technology (KAIST)
Jaehyun Shin: Innovation, AKQA
Jae-Hun Lee: Institute for Basic Science (IBS)
Woori Kim: Harvard Medical School
Jea Kwon: Max Planck Institute for Security and Privacy (MPI-SP)
Heeyoung Lee: Korea Advanced Institute of Science and Technology (KAIST)
Dae-gun Kim: KAIST
Choong Yeon Kim: KAIST
Sian Choi: Korea Advanced Institute of Science and Technology (KAIST)
Jae-Woong Jeong: KAIST
Kwang-Soo Kim: Harvard Medical School
C. Justin Lee: Institute for Basic Science (IBS)
Daesoo Kim: KAIST
Won Do Heo: Korea Advanced Institute of Science and Technology (KAIST)

Nature Communications, 2025, vol. 16, issue 1, 1-19

Abstract: Abstract Parkinson’s disease (PD), a progressive neurodegenerative disorder, presents complex motor symptoms and lacks effective disease-modifying treatments. Here we show that integrating artificial intelligence (AI) with optogenetic intervention, termed optoRET, modulating c-RET (REarranged during Transfection) signalling, enables task-independent behavioural assessments and therapeutic benefits in freely moving male AAV-hA53T mice. Utilising a 3D pose estimation technique, we developed tree-based AI models that detect PD severity cohorts earlier and with higher accuracy than conventional methods. Employing an explainable AI technique, we identified a comprehensive array of PD behavioural markers, encompassing gait and spectro-temporal features. Moreover, our AI-driven analysis highlights that optoRET effectively alleviates PD progression by improving limb coordination and locomotion and reducing chest tremor. Our study demonstrates the synergy of integrating AI and optogenetic techniques to provide an efficient diagnostic method with extensive behavioural evaluations and sets the stage for an innovative treatment strategy for PD.

Date: 2025
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DOI: 10.1038/s41467-025-63025-w

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