Optogenetic Inactivation of the Subthalamic Nucleus Improves Forelimb Akinesia in a Rat Model of Parkinson Disease

Yoon, Hyun Soo; Park, Jin Hoon; Kim, Yong Hwan; Min, Joongkee; Hwang, Eunmi; Lee, C. Justin; Suh, Jin‐Yoo; Hwang, Onyou; Jeon, Sang Ryong

doi:10.1227/neu.0000000000000297

Cited by 75 publications

(64 citation statements)

References 35 publications

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“…This is not unlike lesion therapy in PD [26]. Interestingly, inhibitory optogenetic STN stimulation alleviated motor symptoms in a rodent model of PD [27] (although an earlier study failed to find a similar effect [28]). …”

Section: A Electrical Vs Optogenetic Stimulation: Efficacy and Mechmentioning

confidence: 98%

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia

Ratnadurai-Giridharan

Cheung

Rubchinsky

2017

IEEE Trans. Neural Syst. Rehabil. Eng.

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Abstract-Conventional deep brain stimulation (DBS) of basal ganglia uses high-frequency regular electrical pulses to treat Parkinsonian motor symptoms and has a series of limitations. Relatively new and not yet clinically tested optogenetic stimulation is an effective experimental stimulation technique to affect pathological network dynamics. We compared the effects of electrical and optogenetic stimulation of the basal ganglia on the pathological parkinsonian rhythmic neural activity. We studied the network response to electrical stimulation and excitatory and inhibitory optogenetic stimulations. Different stimulations exhibit different interactions with pathological activity in the network. We studied these interactions for different network and stimulation parameter values. Optogenetic stimulation was found to be more efficient than electrical stimulation in suppressing pathological rhythmicity. Our findings indicate that optogenetic control of neural synchrony may be more efficacious than electrical control because of the different ways of how stimulations interact with network dynamics.

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Section: A Electrical Vs Optogenetic Stimulation: Efficacy and Mechmentioning

confidence: 98%

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia

Ratnadurai-Giridharan

Cheung

Rubchinsky

2017

IEEE Trans. Neural Syst. Rehabil. Eng.

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“…This cell type specificity allows manipulation of specific circuits and thus more targeted manipulations, which should help pinpoint the circuits and molecular mechanisms that underlie diseases. Optogenetic approaches have been used in rodents to probe neural circuits for several neurological/neurodegenerative diseases, including Parkinson's disease [78,79], epilepsy [80,81], and stroke [26,82]. In the next sections we will first introduce optogenetics and its developments, and then review the current understanding of remapping and recovery after stroke from recent studies using peripheral and optogenetic stimulation, as well as the use of optogenetic stimulation to enhance post-stroke recovery.…”

Section: Current Brain Stimulation Techniques Used To Study Stroke Rementioning

confidence: 99%

“…Furthermore, optogenetics has been widely used to study Parkinson's disease. Optogenetic inhibition of the subthalamic nucleus improved 6-hydroxydopamine-induced Parkinson symptoms such as forelimb akinesia [79]. Optogenetics is also useful for dissecting more complex neural circuits of behavior such as in the psychiatric diseases of depression, addiction, and autism [135].…”

Section: Optogenetic Studies In Various Disease Modelsmentioning

confidence: 99%

“…Optogenetic techniques have been used widely to study disease mechanisms, particularly in preclinical neuropsychiatric and neurological disorders [26,[78][79][80][81][82]. The major advantage of the optogenetics technique is its specific cell type circuit manipulations with temporal precision, which is difficult to achieve with existing brain stimulation techniques, such as deep brain stimulation, TMS, and tDCS [76,77].…”

Section: Translational Potential Of Optogenetics and Limitationsmentioning

confidence: 99%

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Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

2016

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Stroke is a leading cause of death and disability in the USA, yet treatment options are very limited. Functional recovery can occur after stroke and is attributed, in part, to rewiring of neural connections in areas adjacent to or remotely connected to the infarct. A better understanding of neural circuit rewiring is thus an important step toward developing future therapeutic strategies for stroke recovery. Because stroke disrupts functional connections in peri-infarct and remotely connected regions, it is important to investigate brain-wide network dynamics during post-stroke recovery. Optogenetics is a revolutionary neuroscience tool that uses bioengineered lightsensitive proteins to selectively activate or inhibit specific cell types and neural circuits within milliseconds, allowing greater specificity and temporal precision for dissecting neural circuit mechanisms in diseases. In this review, we discuss the current view of post-stroke remapping and recovery, including recent studies that use optogenetics to investigate neural circuit remapping after stroke, as well as optogenetic stimulation to enhance stroke recovery. Multimodal approaches employing optogenetics in conjunction with other readouts (e.g., in vivo neuroimaging techniques, behavior assays, and next-generation sequencing) will advance our understanding of neural circuit reorganization during post-stroke recovery, as well as provide important insights into which brain circuits to target when designing brain stimulation strategies for future clinical studies.

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“…Chloride pump halorhodopsin can be transfected using adeno-associated virus (AAV) in the target region when illuminated with yellow light (wavelength, 590 nm), resulting in hyperpolarization and inhibition from firing action potential [11]. Recently, we provided evidence that optogenetic subthalamic nucleus (STN) inactivation improves the akinesia observed in a rat model of Parkinson's disease [12]. In the present study, we applied optogenetics to the treatment of levodopa-induced dyskinesia (LID), which is another treatment target of DBS.…”

Section: Introductionmentioning

confidence: 99%

Optogenetic Inhibition of the Subthalamic Nucleus Reduces Levodopa-Induced Dyskinesias in a Rat Model of Parkinson's Disease

Yoon

Min

Hwang

et al. 2016

Stereotact Funct Neurosurg

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Background: The inhibition of neuronal activity by electrical deep brain stimulation is one of the mechanisms explaining the amelioration of levodopa-induced dyskinesia. However, electrical deep brain stimulation cannot specifically activate or inactivate selected types of neurons. Objectives: We applied optogenetics as an alternative treatment to deep brain stimulation for levodopa-induced dyskinesia, and also to confirm that the mechanism of levodopa-induced dyskinesia amelioration by subthalamic nucleus deep brain stimulation is mediated through neuronal inhibition. Methods: 6-hydroxydopamine-induced hemiparkinsonian rats received injections of hSynapsin1-NpHR-YFP adeno-associated virus (AAV) or hSynapsin1-YFP AAV. Two weeks after viral injections, all rats were treated with daily injections of levodopa. Then, the optic fiber was implanted into the ipsilateral subthalamic nucleus. We performed various behavioral tests to evaluate the changes in levodopa-induced dyskinesias after optogenetic expression and illumination in the subthalamic nucleus. Results: The behavioral tests revealed that optical inhibition of the subthalamic nucleus significantly ameliorated levodopa-induced dyskinesia by reducing the duration of the dyskinesias as well as the severity of axial dyskinesia. Conclusions: These findings will provide a useful foundation for the future development of optogenetic modulation systems that could be considered as an approach to dyskinesia therapy.

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Optogenetic Inactivation of the Subthalamic Nucleus Improves Forelimb Akinesia in a Rat Model of Parkinson Disease

Abstract: 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.

Cited by 75 publications

References 35 publications

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia

Effects of Electrical and Optogenetic Deep Brain Stimulation on Synchronized Oscillatory Activity in Parkinsonian Basal Ganglia

Optogenetic Approaches to Target Specific Neural Circuits in Post-stroke Recovery

Optogenetic Inhibition of the Subthalamic Nucleus Reduces Levodopa-Induced Dyskinesias in a Rat Model of Parkinson's Disease

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