The DOI matches its Crossref record; 43 of the 43 references it cites were found in a registry or an index.
Repeated Cortico-Striatal Stimulation Generates Persistent OCD-Like Behavior
Open accessAbstract
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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“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]
In the citing paper
“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]
In the citing paper
“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]
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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
In the citing paper
“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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Cites
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Gorski, J. A., Talley, T., Qiu, M. S., Puelles, L., Rubenstein, J. L. R., & Jones, K. R. (2002) · Journal of Neuroscience · doi:10.1523/jneurosci.22-15-06309.2002 · Cited by 1,403
Phasic Firing in Dopaminergic Neurons Is Sufficient for Behavioral Conditioning
Tsai, H.-C., Zhang, F., Adamantidis, A., Stuber, G. D., Bonci, A., de Lecea, L., & Deisseroth, K. (2009) · Science · doi:10.1126/science.1168878 · Cited by 1,266
Self-citationMenzies, L., Chamberlain, S. R., Laird, A. R., Thelen, S. M., Sahakian, B. J., & Bullmore, E. T. (2008) · Neuroscience & Biobehavioral Reviews · doi:10.1016/j.neubiorev.2007.09.005 · Cited by 1,190
Practice Guideline for the Treatment of Patients With Obsessive-Compulsive Disorder
(2008) · APA Practice Guidelines for the Treatment of Psychiatric Disorders: Comprehensive Guidelines and Guideline Watches · doi:10.1176/appi.books.9780890423363.149114 · Cited by 1,028
Self-citationMataix-Cols, D., Wooderson, S., Lawrence, N., Brammer, M. J., Speckens, A., & Phillips, M. L. (2004) · Archives of General Psychiatry · doi:10.1001/archpsyc.61.6.564 · Cited by 929
Greenberg, B. D., Gabriels, L. A., Malone, D. A., Rezai, A. R., Friehs, G. M., Okun, M. S., Shapira, N. A., Foote, K. D., Cosyns, P. R., Kubu, C. S., et al. (2010) · Molecular Psychiatry · doi:10.1038/mp.2008.55 · Cited by 867
Toward a neurobiology of obsessive-compulsive disorder
Graybiel, A. M., & Rauch, S. L. (2000) · Neuron · doi:10.1016/s0896-6273(00)00113-6 · Cited by 864
Cortico-striatal synaptic defects and OCD-like behaviours in Sapap3-mutant mice
Welch, J. M., Lu, J., Rodriguiz, R. M., Trotta, N. C., Peca, J., Ding, J.-D., Feliciano, C., Chen, M., Adams, J. P., Luo, J., et al. (2007) · Nature · doi:10.1038/nature06104 · Cited by 852
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Vandevelde, A., Dollfus, S., & Gagnepain, P. (2026) · Psychiatry and Clinical Neurosciences · doi:10.1111/pcn.70155
B-REAL: A keypoint-less behavior platform for offline classification and real-time detectionPreprint
Yttri, E. A., Eagle, A., Kohler, B., Kamrowski, V., Li, R., & Li, R. (2026) · Research Square · doi:10.64898/2026.10.13.758637
Metadata
- 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 › Clinical Neurology › Deep Brain Stimulation and Movement Disorders
- 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
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