Ahead of Print: Optogenetic Inactivation Improves Forelimb Akinesia

Background: The inhibition of neuronal activity by electrical deep brain stimulation (DBS) is one of the mechanisms explaining therapeutic effects on Parkinson’s disease (PD) patients 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: We performed various behavioral tests to evaluate changes in motor functions in a PD rat model after optogene expression. Unlike previous studies, we assessed the therapeutic effects of direct optogenetic inactivation in the STN.

Methods: 6-hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats received injections of hSynapsin1-NpHR-YFP AAV or an equivalent volume of PBS. Three weeks after injection of AAV or PBS, the optic fiber was implanted into the ipsilateral STN. Stepping test, cylinder test, and apomorphine-induced rotation test were performed in three sequential steps: during light-off state, light stimulation, and light-off state.

Results: Stepping tests revealed that optical inhibition of the STN significantly improved 6-OHDA-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 co-localized 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.

From: Optogenetic Inactivation of the Subthalamic Nucleus Improves Forelimb Akinesia in a Rat Model of Parkinson’s Disease by Yoon et al.

Full article access for Neurosurgery subscribers at Neurosurgery-Online.com.