Repeated cortico-striatal stimulation generates persistent OCD-like behavior Academic Article uri icon

Overview

MeSH Major

  • Corpus Striatum
  • Frontal Lobe
  • Obsessive-Compulsive Disorder
  • Thalamus

abstract

  • 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.

publication date

  • January 2013

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3954809

Digital Object Identifier (DOI)

  • 10.1126/science.1234733

PubMed ID

  • 23744948

Additional Document Info

start page

  • 1234

end page

  • 9

volume

  • 340

number

  • 6137