Repeated cortico-striatal stimulation generates persistent OCD-like behavior
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What Causes Obsessive Compulsive Disorder?: Obsessive compulsive disorder is a severe, chronic mental illness that affects millions of individuals. However, the mechanisms underlying this disease are still largely unknown (see the Perspective by Rauch and Carlezon Jr. ). Ahmari et al. (p. 1234 ) stimulated glutamatergic pathways between the orbitofrontal cortex and the ventromedial striatum and used grooming to assess obsessive compulsive behavior in mice. Repetitive stimulation over days triggered changes in the neuronal responses of the ventromedial striatum. Over time, the behavior of the animals became independent of stimulation and could be prevented by the antidepressant fluoxetine. Burguière et al. (p. 1243 ) investigated the neural basis of obsessive compulsive symptoms in a mutant mouse that showed excessive expression of a conditioned form of grooming.
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Hyperactivity in the OFC-striatum pathway plays a pivotal role in the pathology of compulsivity.
“Accumulating evidence from animal and clinical research has shown that hyperactivity in the OFC-striatum pathway plays a pivotal role in the pathology of compulsivity64–66.”
From Dissociable roles of prefrontal plasticity in decision-making strategy and execution of habitual behavior (2026) · cites this paper as [64]
Ahmari et al found that acute stimulation did not generate repetitive behaviors, but repeated hyperactivation for multiple days led to a progressive and persistent increase in grooming that correlated with increased evoked-firing rate at OFC-VMS synapses.
“While acute stimulation did not generate repetitive behaviors, repeated hyperactivation for multiple days in a row led to a progressive and persistent increase in grooming that correlated with an increased evoked-firing rate at OFC-VMS synapses.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [105]
Increased grooming and evoked firing in Ahmari et al were both reversed by chronic fluoxetine treatment.
“Increased grooming and evoked firing were both reversed by chronic fluoxetine treatment.”
From DISSECTING OCD CIRCUITS: FROM ANIMAL MODELS TO TARGETED TREATMENTS: Review: Dissecting OCD Circuits: Animals to Treatments (2015) · cites this paper as [105]
Brief, repeated optogenetic stimulation of mOFC terminals in the ventral striatum progressively led to development of repetitive grooming behavior that may be relevant to OCD in mice.
“Brief, repeated, optogenetic stimulation of mOFC terminals in VS progressively led to the development of repetitive grooming behavior that may be relevant to OCD (Ahmari et al., 2013).”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Ahmari et al., 2013
A circuit-level manipulation of OFC-ventral striatal projections produces OCD-like behaviors in mice.
“While these findings demonstrate that a circuit-level manipulation of OFC-VS projections produces OCD-like behaviors in mice (Ahmari et al., 2013)”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Ahmari et al., 2013
Abnormal functional connectivity in the mOFC-ventral striatal connection could underlie pathological repetitive behaviors.
“Together, these data suggest that abnormal functional connectivity in this interregional connection could underlie pathological repetitive behaviors (Ahmari et al., 2013).”
From A framework for understanding the emerging role of corticolimbic-ventral striatal networks in OCD-associated repetitive behaviors (2015) · cites this paper as Ahmari et al., 2013
Both grooming behaviour and the hyperactivity induced through chronic optogenetic stimulation were remediated using fluoxetine.
“Moreover, they found that both grooming behaviour and the hyperactivity induced through chronic optogenetic stimulation were remediated using a common treatment for OCD, the selective-serotonin reuptake inhibitor fluoxetine (Ahmari et al., 2013).”
From The role of habit in compulsivity (2016) · cites this paper as Ahmari et al., 2013
Chronic optogenetic stimulation of the OFC-ventromedial striatal circuit in otherwise healthy mice produced a causal relationship between hyperactivity and the onset of compulsive grooming behaviour.
“They found that a causal relationship between this hyperactivity and the onset of compulsive grooming behaviour in otherwise healthy mice.”
From The role of habit in compulsivity (2016) · cites this paper as Ahmari et al., 2013
Compulsive grooming can be induced by optogenetically increasing medial/ventral OFC-to-DS pathway activity.
“Compulsive grooming can be induced by optogenetically increasing medial/ventral OFC-to-DS pathway activity [49].”
From Projection-specific deficits in synaptic transmission in adult Sapap3-knockout mice (2020) · cites this paper as [49]
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Abnormal Striatal Development Underlies the Early Onset of Behavioral Deficits in Shank3B Mice
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- Authors
- Ahmari, S. E., Spellman, T., Douglass, N. L., Kheirbek, M. A., Simpson, H. B., Deisseroth, K., Gordon, J. A., & Hen, R.
- Affiliations
- New York State Psychiatric Institute (US)
- Columbia University Irving Medical Center (US)
- Stanford Medicine (US)
- Corresponding author
- Ahmari, Susanne E.
- ORCID
- Venue
- Science
- Published
- 2013-06-07
- Volume
- 340
- Issue
- 6137
- Pages
- 1234-1239
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC3954809
- OpenAlex
- W2003956812
- Cited by
- 502
- References
- 43
- Citations by year
- 2026: 27 · 2025: 34 · 2024: 26 · 2023: 26 · 2022: 38 · 2021: 43 · 2020: 47 · 2019: 47 · 2018: 30 · 2017: 44 · 2016: 41 · 2015: 53 · 2014: 33 · 2013: 11
- FWCI
- 51.12
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (5r01mh096274-06)
- National Institute of Mental Health (K24MH091555, R01-MH096274, K01MH099371, K08MH087718)
- Topics
- Social Sciences › Psychology › Clinical Psychology › Obsessive-Compulsive Spectrum Disorders
- Health Sciences › Medicine › Neurology › Neurological disorders and treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- obsessive-compulsive disorder, cortico-striato-thalamo-cortical circuit, orbitofrontal cortex, ventromedial striatum, grooming, fluoxetine, optogenetics, mouse model
- MeSH terms
- Channelrhodopsins, Adenoviridae, Animals, Bacterial Proteins, Behavior, Animal, Corpus Striatum, Electric Stimulation, Fluoxetine, Frontal Lobe, Luminescent Proteins, Male, Obsessive-Compulsive Disorder, Thalamus, Selective Serotonin Reuptake Inhibitors, Artificial Gene Fusion, Mice, Optogenetics
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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