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

Proceedings of the National Academy of Sciences of the United States of America
Tingting SunZhi Zhang

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.

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Citations

Dec 5, 2019·The International Journal of Neuropsychopharmacology·Hector E YarurKatia Gysling
Mar 7, 2020·Frontiers in Pharmacology·Angélica Del Pilar EscobarJosé Antonio Fuentealba
Dec 13, 2019·Pharmacological Reviews·Henry SzechtmanKurt Leroy Hoffman
Dec 2, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xiao-Yang ZhangJing-Ning Zhu
Feb 2, 2021·Frontiers in Cellular Neuroscience·Tanya Gandhi, Charles C Lee
Jul 9, 2021·Frontiers in Cellular Neuroscience·Angélica P EscobarPablo R Moya
Dec 4, 2021·Molecular Therapy : the Journal of the American Society of Gene Therapy·Jingwei SongMichael Michaelides

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