ArticleNeurobiology of disease2016
Optogenetic stimulation of cortico-subthalamic projections is sufficient to ameliorate bradykinesia in 6-ohda lesioned mice.
Article in Neurobiology of disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers, 1 of them a synthesis that pooled it.
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Who cites it
67 citing papers in PubMed, 1 synthesis or guideline pooled it, 138 citations in OpenAlex.
- Deep Brain Stimulation of the Subthalamic Nucleus Modulates Reward-Related Behavior: A Systematic Review.Frontiers in human neuroscience · 2020Pooled it
- Mechanism and progress of deep brain stimulation in the treatment of neurological and psychiatric disorders.MedScience · 2026Review
- Lifespan dynamics of STN-based functional connectivity and network properties: Implications for motor dysfunction and circuit-based neuromodulation.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Deep Brain Stimulation: Mechanisms, Cost-Effectiveness, and Precision Applications Across Neurology and Psychiatry.Biomedicines · 2025Review
- Restoration of locomotor function following stimulation of the A13 region in Parkinson's mouse models.eLife · 2025Article
- Neural pathway activation in the subthalamic region depends on stimulation polarity.Brain communications · 2025Article
- Modeling the modulation of beta oscillations in the basal ganglia by dual-target optogenetic stimulation.Fundamental research · 2025Article
- Why so slow? Models of parkinsonian bradykinesia.Nature reviews. Neuroscience · 2024Review
- Dysfunction of motor cortices in Parkinson's disease.Cerebral cortex (New York, N.Y. : 1991) · 2024Review
- Neural signatures of indirect pathway activity during subthalamic stimulation in Parkinson's disease.Nature communications · 2024Article
- Does Vestibular Motion Perception Correlate with Axonal Pathways Stimulated by Subthalamic Deep Brain Stimulation in Parkinson's Disease?Cerebellum (London, England) · 2024Article
- Modulation of DBS-induced cortical responses and movement by the directionality and magnitude of current administered.NPJ Parkinson's disease · 2024Article
- Neuronal and synaptic adaptations underlying the benefits of deep brain stimulation for Parkinson's disease.Translational neurodegeneration · 2023Review
- Neurophysiological mechanisms of deep brain stimulation across spatiotemporal resolutions.Brain : a journal of neurology · 2023Review
- Review
- Influence of charges deposited on membranes of human hyperdirect pathway axons on depolarization during subthalamic deep brain stimulation.Journal of neural engineering · 2023Article
- The Therapeutic Frequency Profile of Subthalamic Nucleus Deep Brain Stimulation in Rats Is Shaped by Antidromic Spike Failure.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Coenzyme QScientific reports · 2023Article
- DBS-evoked cortical responses index optimal contact orientations and motor outcomes in Parkinson's disease.NPJ Parkinson's disease · 2023Article
- Controlling pathological activity of Parkinson basal ganglia based on excitation and inhibition optogenetic models and monophasic and biphasic electrical stimulations.Journal of biosciences · 2023Article
7 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Electrical deep brain stimulation (DBS) of the subthalamic nucleus (STN) is effective for ameliorating the motor symptoms of Parkinson's disease (PD) including bradykinesia. The STN receives its main excitatory input from cortex; however, the contribution of cortico-subthalamic projection neurons to the effects of DBS remains unclear. To isolate the consequences of stimulating layer 5 primary motor cortex (M1) projections to the STN, we used a dual virus transfection technique to selectively express opsins in these neurons in mice made parkinsonian by unilateral nigrostriatal 6-OHDA lesioning. AAVs containing WGA-Cre constructs were injected in the STN to retrogradely place Cre in STN afferents, while AAVs containing Cre-dependent ultrafast hChR2(E123T/T159C)-EYFP opsin constructs were injected in M1 layer 5, producing specific opsin expression in M1-STN projections. Under unstimulated conditions, lesioned mice showed bradykinesia and hypokinesia (decreased movement), along with electrophysiological changes similar to those observed in PD patients. Specifically, low frequency power (theta, alpha, low beta) was increased and gamma power was decreased, while M1/STN coherence and STN phase-amplitude-coupling (PAC) were increased. Optogenetic stimulation (100-130Hz) of STN afferents in these mice ameliorated bradykinesia and hypokinesia and brought the neural dynamics closer to the non-parkinsonian state by reducing theta and alpha and increasing gamma power in M1, decreasing STN PAC, and reducing theta band coherence. Histological examination of the EYFP expression revealed that, in addition to orthodromic and antidromic effects, stimulation of cortico-subthalamic neurons may cause wide-spread increased glutamatergic activity due to collaterals that project to areas of the thalamus and other brain regions.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.