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Related Experiment Video

Updated: May 10, 2026

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

Signal Attenuation as a Rat Model of Obsessive Compulsive Disorder

Published on: January 9, 2015

Repeated cortico-striatal stimulation generates persistent OCD-like behavior.

Susanne E Ahmari¹, Timothy Spellman, Neria L Douglass

¹Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA. sea2103@columbia.edu

Science (New York, N.Y.)

|June 8, 2013

Summary

This summary is machine-generated.

Repeated optogenetic stimulation of the cortico-striato-thalamo-cortical (CSTC) circuit in mice induced persistent grooming behaviors, mimicking obsessive compulsive disorder (OCD) symptoms. This circuit hyperactivity was reversed by fluoxetine treatment.

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Area of Science:

Neuroscience
Psychiatry
Computational Neuroscience

Background:

Cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is linked to obsessive compulsive disorder (OCD).
Direct causal links between CSTC hyperactivity and OCD cannot be ethically tested in humans.

Purpose of the Study:

To investigate the causal role of CSTC circuit hyperactivation in the development of repetitive behaviors relevant to OCD.
To explore the effects of repeated, simulated CSTC hyperactivation on behavior and neural activity in a mouse model.

Main Methods:

Utilized optogenetics in mice to repeatedly stimulate the orbitofrontal cortex (OFC)-ventromedial striatum (VMS) pathway, simulating CSTC hyperactivation.
Monitored behavioral changes, specifically grooming frequency, and recorded light-evoked neuronal firing in the VMS.
Administered chronic fluoxetine, a standard OCD treatment, to assess its impact on behaviors and neural activity.

Main Results:

Acute OFC-VMS stimulation did not induce repetitive behaviors.
Repeated daily stimulation over multiple days progressively increased grooming behavior, which persisted for two weeks post-stimulation.
This persistent grooming was associated with increased light-evoked firing in postsynaptic VMS neurons.
Chronic fluoxetine treatment reversed both the increased grooming and the enhanced VMS neuronal firing.

Conclusions:

Brief, repeated episodes of abnormal CSTC circuit activity can establish persistent behavioral changes resembling OCD.
This study provides a potential causal mechanism linking CSTC circuit dysfunction to the development of enduring psychopathology.
The findings support the therapeutic efficacy of fluoxetine in modulating circuit activity and associated behaviors in OCD.