Frequency-Specific Optogenetic Deep Brain Stimulation of Subthalamic Nucleus Improves Parkinsonian Motor Behaviors
| Autor: | Isaac R. Cassar, Warren M. Grill, Chunxiu Yu, Jaydeep Sambangi |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Parkinson's disease Deep brain stimulation medicine.medical_treatment Deep Brain Stimulation Movement Stimulation Substantia nigra Optogenetics Globus Pallidus Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Parkinsonian Disorders Subthalamic Nucleus medicine Animals Evoked Potentials Research Articles Opsins business.industry General Neuroscience Parkinsonism medicine.disease nervous system diseases Rats Substantia Nigra Subthalamic nucleus 030104 developmental biology Globus pallidus surgical procedures operative nervous system Female business Beta Rhythm Neuroscience therapeutics 030217 neurology & neurosurgery |
| Zdroj: | J Neurosci |
| ISSN: | 1529-2401 |
| Popis: | Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is an effective therapy for the motor symptoms of Parkinson's disease (PD). However, the neural elements mediating symptom relief are unclear. A previous study concluded that direct optogenetic activation of STN neurons was neither necessary nor sufficient for relief of parkinsonian symptoms. However, the kinetics of the channelrhodopsin-2 (ChR2) used for cell-specific activation are too slow to follow the high rates required for effective DBS, and thus the contribution of activation of STN neurons to the therapeutic effects of DBS remains unclear. We quantified the behavioral and neuronal effects of optogenetic STN DBS in female rats following unilateral 6-hydroxydopamine (6-OHDA) lesion using an ultrafast opsin (Chronos). Optogenetic STN DBS at 130 pulses per second (pps) reduced pathologic circling and ameliorated deficits in forelimb stepping similarly to electrical DBS, while optogenetic STN DBS with ChR2 did not produce behavioral effects. As with electrical DBS, optogenetic STN DBS exhibited a strong dependence on stimulation rate; high rates produced symptom relief while low rates were ineffective. High-rate optogenetic DBS generated both increases and decreases in firing rates of single neurons in STN, globus pallidus externa (GPe), and substantia nigra pars reticular (SNr), and disrupted β band oscillatory activity in STN and SNr. High-rate optogenetic STN DBS can indeed ameliorate parkinsonian motor symptoms through reduction of abnormal oscillatory activity in the STN-associated neural circuit, and these results highlight that the kinetic properties of opsins have a strong influence on the effects of optogenetic stimulation.SIGNIFICANCE STATEMENTWhether STN local cells contribute to the therapeutic effects of subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD) remains unclear. We re-examined the role of STN local cells in mediating the symptom-relieving effects of STN DBS using cell type-specific optogenetic stimulation with a much faster opsin, Chronos. Direct optogenetic stimulation of STN neurons was effective in treating the symptoms of parkinsonism in the 6-hydroxydopamine (6-OHDA) lesion rat. These results highlight that the kinetic properties of opsins can have a strong influence on the effects of optogenetic activation/inhibition and must be considered when employing optogenetic to study high-rate neural stimulation. |
| Databáze: | OpenAIRE |
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