Neuron type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct.

1. Exp Mol Med. 2024 Jun;56(6):1439-1449. doi: 10.1038/s12276-024-01253-8. Epub 2024 Jun 3.

Neuron type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct.

Kim RG(#)(1)(2), Cho J(#)(1), Park JY(1), Kim YR(3), Lee MC(4), Kim HI(5)(6).

Author information: (1)Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, 123 Choemdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea. (2)Research Headquarter, Korea Brain Research Institute, 61 Cheomdan-ro, Dong-gu, Daegu, 41062, Republic of Korea. (3)Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA, 02129, USA. (4)Pathology Center, Seegene Medical Foundation, 320 Cheonho-Daero, Seongdong-gu, Seoul, 04805, Republic of Korea. (5)Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, 123 Choemdangwagi-ro, Buk-gu, Gwangju, 61005, Republic of Korea. hyoungihl@gist.ac.kr. (6)Department of Neurosurgery, Presbyterian Medical Center, 365 Seowon-ro, Wansan-gu, Jeonju-si, Jeollabuk-do, 54987, Republic of Korea. hyoungihl@gist.ac.kr. (#)Contributed equally

Cortical neuromodulation (CNM) is widely used to promote recovery after stroke. Despite the beneficial results of CNM, the roles played by different neuron types in the effects of current CNM techniques are unable to be differentiated. Our aim was to use selective optogenetic cortical stimulation to explore how different subpopulations of neuronal cells contribute to poststroke recovery. We transduced the sensory-parietal cortex (SPC) of rats with CamKII-ChR2 (pyramidal neurons), PV-ChR2 (parvalbumin-expressing inhibitory neurons), or hSyn-ChR2 (pan-neuronal population) before inducing photothrombotic capsular infarct lesions. We found that selective stimulation of inhibitory neurons resulted in significantly greater motor recovery than stimulation of excitatory neurons or the pan-neuronal population. Furthermore, 2-deoxy-2-[18F] fluoro-D-glucose microPET (FDG-microPET) imaging revealed a significant reduction in cortical diaschisis and activation of the corticostriatal neural circuit, which were correlated with behavioral recovery in the PV-ChR2 group. The spatial pattern of brain-derived neurotrophic factor (BDNF) expression was evident in the stimulated cortex and underlying cortico-subcortical circuit. Our results indicate that the plasticity of inhibitory neurons is crucial for functional recovery after capsular infarct. Modifying CNM parameters to potentiate the stimulation of inhibitory neurons could improve poststroke outcomes.

© 2024. The Author(s).

DOI: 10.1038/s12276-024-01253-8 PMCID: PMC11263592 PMID: 38825647 [Indexed for MEDLINE]

Conflict of interest statement: The authors declare no competing interests.