Optogenetic inactivation of the subthalamic nucleus improves forelimb akinesia in a rat model of parkinson disease

Hyung Ho Yoon, Jin Hoon Park, Yong Hwan Kim, Joongkee Min, Eunmi Hwang, C. Justin Lee, Jun Kyo Francis Suh, Onyou Hwang, Sang Ryong Jeon

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

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 phosphatebuffered saline. Three weeks after injection of adeno-associated virus or phosphatebuffered 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.

Original languageEnglish
Pages (from-to)533-540
Number of pages8
JournalNeurosurgery
Volume74
Issue number5
DOIs
Publication statusPublished - 2014 May

Keywords

  • Deep brain stimulation
  • Forelimb akinesia
  • Halorhodopsin
  • Optogenetics
  • Parkinson disease
  • Subthalamic nucleus
  • hSynapsin1

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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    Yoon, H. H., Park, J. H., Kim, Y. H., Min, J., Hwang, E., Lee, C. J., Francis Suh, J. K., Hwang, O., & Jeon, S. R. (2014). Optogenetic inactivation of the subthalamic nucleus improves forelimb akinesia in a rat model of parkinson disease. Neurosurgery, 74(5), 533-540. https://doi.org/10.1227/NEU.0000000000000297