ArticleProceedings of the National Academy of Sciences of the United States of America2021
Optogenetic stimulation of glutamatergic neurons in the cuneiform nucleus controls locomotion in a mouse model of Parkinson's disease.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 77 citations in OpenAlex.
- Vestibular nucleus stimulation for ameliorating locomotor dynamics in a Parkinsonian mouse model.Nature communications · 2026Article
- The Parafascicular Role in Updating Action from a Spatial to a Visual Strategy Is Driven by Its Glutamatergic Mesencephalic Locomotor Region Inputs.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Active pixel power control for crosstalk-free all-optical neural interrogation.Nature communications · 2026Article
- Restoration of locomotor function following stimulation of the A13 region in Parkinson's mouse models.eLife · 2025Article
- Cell-type specific sensory and motor activity in the cuneiform nucleus and pedunculopontine nucleus in mice.Scientific reports · 2025Article
- Chronic Chemogenetic Activation of Astrocytes in the Murine Mesopontine Region Leads to Disturbances in Circadian Activity and Movement.International journal of molecular sciences · 2025Article
- Abnormal activity in the brainstem affects gait in a neuromusculoskeletal model.Journal of neuroengineering and rehabilitation · 2025Article
- A deep learning pipeline for three-dimensional brain-wide mapping of local neuronal ensembles in teravoxel light-sheet microscopy.Nature methods · 2025Article
- A framework for translational therapy development in deep brain stimulation.NPJ Parkinson's disease · 2024Review
- Human TRPV1 is an efficient thermogenetic actuator for chronic neuromodulation.Cellular and molecular life sciences : CMLS · 2024Article
- Article
- Tetherless Optical Neuromodulation: Wavelength from Orange-red to Mid-infrared.Neuroscience bulletin · 2024Review
- The Mesencephalic Locomotor Region: Multiple Cell Types, Multiple Behavioral Roles, and Multiple Implications for Disease.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024Review
- Dopamine-sensitive neurons in the mesencephalic locomotor region control locomotion initiation, stop, and turns.Cell reports · 2024Article
- Electrical stimulation of the cuneiform nucleus enhances the effects of rehabilitative training on locomotor recovery after incomplete spinal cord injury.Frontiers in neuroscience · 2024Article
- Distinct Olfactory Bulb-Cortex Neural Circuits Coordinate Cognitive Function in Parkinson's Disease.Research (Washington, D.C.) · 2024Article
- Chemogenetic and optogenetic stimulation of zona incerta GABAergic neurons ameliorates motor impairment in Parkinson's disease.iScience · 2023Article
- Ameliorating parkinsonian motor dysfunction by targeting histamine receptors in entopeduncular nucleus-thalamus circuitry.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Targeting a vulnerable septum-hippocampus cholinergic circuit in a critical time window ameliorates tau-impaired memory consolidation.Molecular neurodegeneration · 2023Article
- Functional contribution of mesencephalic locomotor region nuclei to locomotor recovery after spinal cord injury.Cell reports. Medicine · 2023Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
In Parkinson's disease (PD), the loss of midbrain dopaminergic cells results in severe locomotor deficits, such as gait freezing and akinesia. Growing evidence indicates that these deficits can be attributed to the decreased activity in the mesencephalic locomotor region (MLR), a brainstem region controlling locomotion. Clinicians are exploring the deep brain stimulation of the MLR as a treatment option to improve locomotor function. The results are variable, from modest to promising. However, within the MLR, clinicians have targeted the pedunculopontine nucleus exclusively, while leaving the cuneiform nucleus unexplored. To our knowledge, the effects of cuneiform nucleus stimulation have never been determined in parkinsonian conditions in any animal model. Here, we addressed this issue in a mouse model of PD, based on the bilateral striatal injection of 6-hydroxydopamine, which damaged the nigrostriatal pathway and decreased locomotor activity. We show that selective optogenetic stimulation of glutamatergic neurons in the cuneiform nucleus in mice expressing channelrhodopsin in a Cre-dependent manner in Vglut2-positive neurons (Vglut2-ChR2-EYFP mice) increased the number of locomotor initiations, increased the time spent in locomotion, and controlled locomotor speed. Using deep learning-based movement analysis, we found that the limb kinematics of optogenetic-evoked locomotion in pathological conditions were largely similar to those recorded in intact animals. Our work identifies the glutamatergic neurons of the cuneiform nucleus as a potentially clinically relevant target to improve locomotor activity in parkinsonian conditions. Our study should open avenues to develop the targeted stimulation of these neurons using deep brain stimulation, pharmacotherapy, or optogenetics.
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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.