Journal
SCIENCE
Volume 340, Issue 6137, Pages 1234-1239Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1234733
Keywords
-
Categories
Funding
- National Institute of Mental Health (NIMH) [K08MH087718]
- Louis V. Gerstner, Jr., Scholars Program
- Irving Institute for Clinical and Translational Research
- Gray Matters Foundation
- Leon Levy Foundation
- Brain and Behavior Research Foundation NARSAD Young Investigator Award
- NIMH [K01MH099371]
- Sackler Institute
- NARSAD
- Howard Hughes Medical Institute, NIH, California Institute for Regenerative Medicine
- Defense Advance Research Projects Agency The Reorganization and Plasticity to Accelerate Injury Recovery (REPAIR) Program
- NIH [R01 MH096274]
- Hope for Depression Research Foundation
- International Mental Health Research Organization
Ask authors/readers for more resources
Although cortico-striato-thalamo-cortical (CSTC) circuit dysregulation is correlated with obsessive compulsive disorder (OCD), causation cannot be tested in humans. We used optogenetics in mice to simulate CSTC hyperactivation observed in OCD patients. Whereas acute orbitofrontal cortex (OFC)-ventromedial striatum (VMS) stimulation did not produce repetitive behaviors, repeated hyperactivation over multiple days generated a progressive increase in grooming, a mouse behavior related to OCD. Increased grooming persisted for 2 weeks after stimulation cessation. The grooming increase was temporally coupled with a progressive increase in light-evoked firing of postsynaptic VMS cells. Both increased grooming and evoked firing were reversed by chronic fluoxetine, a first-line OCD treatment. Brief but repeated episodes of abnormal circuit activity may thus set the stage for the development of persistent psychopathology.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available