Yoon, Hyung Ho Park, Jin Hoon Kim, Yong Hwan Min, Joongkee Hwang, Eunmi Lee, C. Justin Suh, Jun-Kyo Francis Hwang, Onyou Jeon, Sang Ryong 2024-01-20T10:00:36Z 2024-01-20T10:00:36Z 2021-09-05 2014-05 0148-396X https://pubs.kist.re.kr/handle/201004/126819 BACKGROUND: The inhibition of neuronal activity by electrical deep brain stimulation is one of the mechanisms explaining the therapeutic effects in patients with Parkinson disease (PD) but cannot specifically activate or inactivate different types of neurons. Recently, a new technology based on optogenetics has been developed to modulate the activity of specific neurons. However, the therapeutic effects of optical inactivation in the subthalamic nucleus (STN) have not been fully investigated. OBJECTIVE: To perform various behavioral tests to evaluate changes in motor functions in a PD rat model after optogene expression and, unlike previous studies, to assess the therapeutic effects of direct optogenetic inactivation in the STN. METHODS: 6-Hydroxydopamine-induced hemiparkinsonian rats received injections of hSynapsin1-NpHR-YFP adeno-associated virus or an equivalent volume of phosphate-buffered saline. Three weeks after injection of adeno-associated virus or phosphate-buffered saline, the optic fiber was implanted into the ipsilateral STN. A stepping test, a cylinder test, and an apomorphine-induced rotation test were performed in 3 sequential steps: during light-off state, during light stimulation, and again during light-off state. RESULTS: Stepping tests revealed that optical inhibition of the STN significantly improved 6-hydroxydopamine-induced forelimb akinesia. PD motor signs, as assessed by cylinder and apomorphine tests, were not affected by optical inhibition. Immunofluorescence revealed that halorhodopsin was highly expressed and colocalized with vesicular glutamate transporter 2 in the STN. CONCLUSION: Optogenetic inhibition in the STN may be effective in improving contralateral forelimb akinesia but not in changing forelimb preference or reducing dopaminergic receptor supersensitivity. These findings are useful as a basis for future studies on optogenetics in PD. English OXFORD UNIV PRESS INC DEEP BRAIN-STIMULATION HIGH-FREQUENCY STIMULATION ADENOASSOCIATED VIRUS NEURAL CIRCUITRY BASAL GANGLIA GENE-THERAPY NEURONS PRIMATES DEGENERATION APOMORPHINE Optogenetic Inactivation of the Subthalamic Nucleus Improves Forelimb Akinesia in a Rat Model of Parkinson Disease Article 10.1227/NEU.0000000000000297 1 NEUROSURGERY, v.74, no.5, pp.533 - 541 NEUROSURGERY 74 5 533 541 scie scopus 000337724800009 2-s2.0-84899642198 Clinical Neurology Surgery Neurosciences & Neurology Surgery Article DEEP BRAIN-STIMULATION HIGH-FREQUENCY STIMULATION ADENOASSOCIATED VIRUS NEURAL CIRCUITRY BASAL GANGLIA GENE-THERAPY NEURONS PRIMATES DEGENERATION APOMORPHINE Deep brain stimulation Forelimb akinesia Halorhodopsin hSynapsin1 Optogenetics Parkinson disease Subthalamic nucleus