Basolateral amygdala input to the medial prefrontal cortex controls obsessive-compulsive disorder-like checking behavior

Proc Natl Acad Sci U S A. 2019 Feb 26;116(9):3799-3804. doi: 10.1073/pnas.1814292116. Epub 2019 Feb 11.

Abstract

Obsessive-compulsive disorder (OCD) affects ∼1 to 3% of the world's population. However, the neural mechanisms underlying the excessive checking symptoms in OCD are not fully understood. Using viral neuronal tracing in mice, we found that glutamatergic neurons from the basolateral amygdala (BLAGlu) project onto both medial prefrontal cortex glutamate (mPFCGlu) and GABA (mPFCGABA) neurons that locally innervate mPFCGlu neurons. Next, we developed an OCD checking mouse model with quinpirole-induced repetitive checking behaviors. This model demonstrated decreased glutamatergic mPFC microcircuit activity regulated by enhanced BLAGlu inputs. Optical or chemogenetic manipulations of this maladaptive circuitry restored the behavioral response. These findings were verified in a mouse functional magnetic resonance imaging (fMRI) study, in which the BLA-mPFC functional connectivity was increased in OCD mice. Together, these findings define a unique BLAGlu→mPFCGABA→Glu circuit that controls the checking symptoms of OCD.

Keywords: BLA; OCD checking symptoms; mPFC; neural circuit.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amygdala / diagnostic imaging
  • Amygdala / metabolism*
  • Amygdala / physiopathology
  • Animals
  • Basolateral Nuclear Complex / diagnostic imaging
  • Basolateral Nuclear Complex / metabolism*
  • Basolateral Nuclear Complex / physiopathology
  • Disease Models, Animal
  • Glutamic Acid / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Mice
  • Neural Pathways / metabolism
  • Neural Pathways / physiopathology
  • Neurons / metabolism*
  • Neurons / pathology
  • Obsessive-Compulsive Disorder / diagnostic imaging
  • Obsessive-Compulsive Disorder / metabolism*
  • Obsessive-Compulsive Disorder / physiopathology
  • Prefrontal Cortex / diagnostic imaging
  • Prefrontal Cortex / metabolism
  • Prefrontal Cortex / physiopathology

Substances

  • Glutamic Acid