Author:
Sun Tingting,Song Zihua,Tian Yanghua,Tian Wenbo,Zhu Chunyan,Ji Gongjun,Luo Yudan,Chen Shi,Wang Likui,Mao Yu,Xie Wen,Zhong Hui,Zhao Fei,Luo Min-Hua,Tao Wenjuan,Wang Haitao,Li Jie,Li Juan,Zhou Jiangning,Wang Kai,Zhang Zhi
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.
Funder
National Natural Science Foundation of China
Strategic Priority Research Program of the Chinese Academy of Science
National Key Research and Development Program of China
Publisher
Proceedings of the National Academy of Sciences
Cited by
43 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献