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김형일Hyoung-Ihl Kim

GIST

Exp. Mol. Med., Jun 03 2024, | https://doi.org/10.1038/s12276-024-01253-8 Neuron type-specific optogenetic stimulation for differential stroke recovery in chronic capsular infarct

Ra Gyung Kim^1,2,6, Jongwook Cho^1,6, Ji-Young Park¹, Young Ro Kim³, Min-Cheol Lee⁴ and Hyoung-Ihl Kim^1,5

¹Department of Biomedical Science and Engineering, Gwangju Institute of Science and Technology, 123 Choemdangwagi-ro, Buk-gu, Gwangju 61005, Republic of Korea.

²Research Headquarter, Korea Brain Research Institute, 61 Cheomdan-ro, Dong-gu, Daegu 41062, Republic of Korea.

³Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital, Charlestown, MA 02129, USA.

⁴Pathology Center, Seegene Medical Foundation, 320 Cheonho-Daero, Seongdong-gu, Seoul 04805, Republic of Korea.

⁵Department of Neurosurgery, Presbyterian Medical Center, 365 Seowon-ro, Wansan-gu, Jeonju-si, Jeollabuk-do 54987, Republic of Korea.

⁶These authors contributed equally: Ra Gyung Kim, Jongwook Cho.

Corresponding author

Correspondence to Hyoung-Ihl Kim.

Abstract

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.

논문정보

형식Research article
게재일2024년 06월 (BRIC 등록일 2024-06-18)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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