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

Obsessive-compulsive disorder (OCD) affects similar to 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 (BLA(Glu)) project onto both medial prefrontal cortex glutamate (mPFC(Glu)) and GABA (mPFC(GABA)) neurons that locally innervate mPFC(Glu) 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 BLA(Glu) 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 BLA(Glu)-> mPFC(GABA -> Glu) circuit that controls the checking symptoms of OCD.