ArticleProceedings of the National Academy of Sciences of the United States of America2015
Targeted ablation of cholinergic interneurons in the dorsolateral striatum produces behavioral manifestations of Tourette syndrome.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers, 2 of them syntheses that pooled it.
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Who cites it
84 citing papers in PubMed, 2 syntheses or guidelines pooled it, 157 citations in OpenAlex.
- Gray matter abnormalities in Tourette Syndrome: a meta-analysis of voxel-based morphometry studies.Translational psychiatry · 2021Pooled it
- Pooled it
- A double-blind, sham-controlled, trial of home-administered rhythmic 10-Hz median nerve stimulation for the reduction of tics, and suppression of the urge-to-tic, in individuals with Tourette syndrome and chronic tic disorder.Journal of neuropsychology · 2023Trial
- Tourette syndrome.Nature reviews. Disease primers · 2026Review
- Altered striosome-matrix distribution and activity of striatal cholinergic interneurons in a model of autism-linked repetitive behaviors.Molecular psychiatry · 2026Article
- A Celsr3 Mutation Linked to Tourette Disorder Disrupts Cortical Dendritic Patterning and Striatal Cholinergic Interneuron Excitability.International journal of molecular sciences · 2025Article
- The Immune/Inflammatory Underpinnings of Neurodevelopmental Disorders and Pediatric Acute-Onset Neuropsychiatric Syndrome: A Scoping Review.International journal of molecular sciences · 2025Article
- Interneuron Loss and Microglia Activation by Transcriptome Analyses in the Basal Ganglia of Tourette Disorder.Biological psychiatry · 2025Article
- Article
- Elevated antibody binding to striatal cholinergic interneurons in patients with pediatric acute-onset neuropsychiatric syndrome.Brain, behavior, and immunity · 2024Article
- A mismatch between striatal cholinergic pauses and dopaminergic reward prediction errors.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Activation of MBritish journal of pharmacology · 2024Article
- Pediatric Acute-Onset Neuropsychiatric Syndrome (PANS) and Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS): Immunological Features Underpinning Controversial Entities.Children (Basel, Switzerland) · 2024Review
- Human mutations in high-confidence Tourette disorder genes affect sensorimotor behavior, reward learning, and striatal dopamine in mice.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The role of neuroactive steroids in tic disorders.Neuroscience and biobehavioral reviews · 2024Review
- A novel naïve Bayes approach to identifying grooming behaviors in the force-plate actometric platform.Journal of neuroscience methods · 2024Article
- Striatal insights: a cellular and molecular perspective on repetitive behaviors in pathology.Frontiers in cellular neuroscience · 2024Review
- A comparison of machine learning methods for quantifying self-grooming behavior in mice.Frontiers in behavioral neuroscience · 2024Article
- Sex differences in the distribution and density of regulatory interneurons in the striatum.Frontiers in cellular neuroscience · 2024Article
- Pathway-specific alterations in striatal excitability and cholinergic modulation in a SAPAP3 mouse model of compulsive motor behavior.Cell reports · 2023Article
24 more citing papers are in PubMed but not listed here.
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Gilles de la Tourette syndrome (TS) is characterized by tics, which are transiently worsened by stress, acute administration of dopaminergic drugs, and by subtle deficits in motor coordination and sensorimotor gating. It represents the most severe end of a spectrum of tic disorders that, in aggregate, affect ∼ 5% of the population. Available treatments are frequently inadequate, and the pathophysiology is poorly understood. Postmortem studies have revealed a reduction in specific striatal interneurons, including the large cholinergic interneurons, in severe disease. We tested the hypothesis that this deficit is sufficient to produce aspects of the phenomenology of TS, using a strategy for targeted, specific cell ablation in mice. We achieved ∼ 50% ablation of the cholinergic interneurons of the striatum, recapitulating the deficit observed in patients postmortem, without any effect on GABAergic markers or on parvalbumin-expressing fast-spiking interneurons. Interneuron ablation in the dorsolateral striatum (DLS), corresponding roughly to the human putamen, led to tic-like stereotypies after either acute stress or d-amphetamine challenge; ablation in the dorsomedial striatum, in contrast, did not. DLS interneuron ablation also led to a deficit in coordination on the rotorod, but not to any abnormalities in prepulse inhibition, a measure of sensorimotor gating. These results support the causal sufficiency of cholinergic interneuron deficits in the DLS to produce some, but not all, of the characteristic symptoms of TS.
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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.