ArticleThe Journal of clinical investigation2017
Chemogenetic stimulation of striatal projection neurons modulates responses to Parkinson's disease therapy.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
78 citing papers in PubMed, 1 synthesis or guideline pooled it, 145 citations in OpenAlex.
- The Signaling and Pharmacology of the Dopamine D1 Receptor.Frontiers in cellular neuroscience · 2021Pooled it
- Aberrant Gamma Oscillations in Parkinson's Disease.Neuroscience bulletin · 2026Review
- Overview of the DREADDs chemogenetics and the patent landscape of their actuators.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- Next-generation chemogenetic inhibition using a brain-permeant non-prescription agent.Signal transduction and targeted therapy · 2026Article
- Indirect Striatal Projection Neurons Drive a D2 Receptor-Dependent Pathway to Dyskinesia and Dystonia.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Article
- Microglial sTREM2 limits dyskinesia and acts on TrkB to support circuit plasticity.bioRxiv : the preprint server for biology · 2026Article
- Effects of chemogenetic inhibition of serotonergic raphe-striatal neurons on L-DOPA-induced behaviors and neurochemistry in a rat model of Parkinson's disease.Acta neuropathologica communications · 2026Article
- Aberrant striatal firing mediates impulsive decision-making in a mouse model of Parkinson's disease.Brain : a journal of neurology · 2026Article
- State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease.Science advances · 2025Article
- Levodopa Disrupts Activity Patterns and Encoding of Movement in Striatal Cholinergic Interneurons of Behaving Mice.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Repetitive Levodopa Treatment Drives Cell Type-Specific Striatal Adaptations Associated With Progressive Dyskinesia in Parkinsonian Mice.bioRxiv : the preprint server for biology · 2025Article
- Hippocampal Inhibitory Interneuron-Specific DREADDs Treatment Alters mTORC1-4E-BP Signaling and Impairs Memory Formation.Journal of neurochemistry · 2025Article
- Striosome Circuitry Stimulation Inhibits Striatal Dopamine Release and Locomotion.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2025Article
- State-dependent modulation of spiny projection neurons controls levodopa-induced dyskinesia in a mouse model of Parkinson's disease.bioRxiv : the preprint server for biology · 2025Article
- A humanized Gs-coupled DREADD for circuit and behavior modulation.Frontiers in cellular neuroscience · 2025Article
- Enhancing striatal acetylcholine facilitates dopamine release and striatal output in parkinsonian mice.Cell & bioscience · 2024Article
- Pharmacological targeting of dopamine D1 or D2 receptors evokes a rapid-onset parkinsonian motor phenotype in mice.The European journal of neuroscience · 2024Article
- Molecular and cellular determinants of L-Dopa-induced dyskinesia in Parkinson's Disease.NPJ Parkinson's disease · 2024Article
- Striatal lateral inhibition regulates action selection in a mouse model of levodopa-induced dyskinesia.bioRxiv : the preprint server for biology · 2024Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) patients experience loss of normal motor function (hypokinesia), but can develop uncontrollable movements known as dyskinesia upon treatment with L-DOPA. Poverty or excess of movement in PD has been attributed to overactivity of striatal projection neurons forming either the indirect (iSPNs) or the direct (dSPNs) pathway, respectively. Here, we investigated the two pathways' contribution to different motor features using SPN type-specific chemogenetic stimulation in rodent models of PD (PD mice) and L-DOPA-induced dyskinesia (LID mice). Using the activatory Gq-coupled human M3 muscarinic receptor (hM3Dq), we found that chemogenetic stimulation of dSPNs mimicked, while stimulation of iSPNs abolished the therapeutic action of L-DOPA in PD mice. In LID mice, hM3Dq stimulation of dSPNs exacerbated dyskinetic responses to L-DOPA, while stimulation of iSPNs inhibited these responses. In the absence of L-DOPA, only chemogenetic stimulation of dSPNs mediated through the Gs-coupled modified rat muscarinic M3 receptor (rM3Ds) induced appreciable dyskinesia in PD mice. Combining D2 receptor agonist treatment with rM3Ds-dSPN stimulation reproduced all symptoms of LID. These results demonstrate that dSPNs and iSPNs oppositely modulate both therapeutic and dyskinetic responses to dopamine replacement therapy in PD. We also show that chemogenetic stimulation of different signaling pathways in dSPNs leads to markedly different motor outcomes. Our findings have important implications for the design of effective antiparkinsonian and antidyskinetic drug therapies.
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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.