Research articleEffect of optogenetic modulation on entopeduncular input affects thalamic discharge and behavior in an AAV2-α-synuclein-induced hemiparkinson rat model

- To test whether optogenetic modulation of the entopeduncular nucleus(EP) could alter parkinsonian behavior or thalamic discharge in a hemiparkinson rat model.
- The globus pallidus internus (GPi) in primates is homologous to the entopeduncular nucleus (EP) in rats.
- The author compared parkinson behavior and recorded in vivo neuronal activity between pre- and post-stimulation in hemiparkinson rat model.
- Optical neuromodulation of the EP can be used to successfully control contralateral forelimb movement and thalamic discharge to alleviate symptoms in an AAV2-α-syn-induced hemiparkinson rat model.

ObjectiveNeuromodulation of the globus pallidus internus(GPi) alleviates Parkinson's disease symptoms. The primate GPi is homologous to the rat entopeduncular nucleus (EP). The aim of the present study was to determine if optogenetic modulation of the EP could alter parkinsonian behavior or thalamic discharge in a hemiparkinson rat model.MethodsWe injected an adeno-associated virus type-2 expressing α-synuclein (AAV2-α-syn) into the substantia nigra pars compacta (SNc) of the right hemisphere and confirmed parkinsonian behavior using an amphetamine-induced rotation test. Then we injected activated or inhibited neurons, using the channelrhodopsin2 (ChR2)/halorhodopsin (NpHR) system in the EP of the hemiparkinson rat model and examined downstream effects in vivo. We assessed alterations in parkinsonian behaviors using the stepping and cylinder tests before, during, and after optogenetic stimulation.ResultsImportantly, optogenetic inhibition of the EP improved parkinsonian motor behaviors. When we monitored thalamic neuronal activity following optogenetic neuromodulation in vivo, and we observed alterations in thalamic discharge The thalamic neuronal activity is increased for optogenetic inhibition stimulation, whereas decreased for optogenetic activation stimulation.ConclusionsTaken together, our data demonstrate that optical neuromodulation of the EP can successfully control contralateral forelimb movement and thalamic discharge in an AAV2-α-synuclein-induced hemiparkinson rat model.