A abies virus tracing system was used for retrograde monosynaptic tracing. hChR2-mCherry and eNpHR3.0-eYFP viruses were used for optogenetic manipulations, hM3D(Gq)-mCherry and hM4D(Gi)-mCherry viruses were used for chemogenetic manipulations. (All viruses were packaged by
BrainVTA)
The viruses used in this article from BrainVTA are in the table below
|
Tracing Helper |
PT-0023 rAAV-Ef1α-DIO-RVG-WPRE-pA
PT-0062 rAAV-Ef1α-DIO-EGFP-2a-TVA-WPRE-pA |
|
RV |
R01002 RV-ENVA-ΔG-DsRed |
|
Optogenetic
|
PT-0002 rAAV-Ef1α-DIO-hChR2 (H134R)-mCherry-WPRE-pA
PT-0003 rAAV-Ef1α-DIO-eNpHR3.0-eYFP-WPRE-pA |
|
Chemogenetics |
PT-0042 rAAV-Ef1α-DIO-hM3D(Gq)-mCherry-WPRE-pA
PT-0043 rAAV-Ef1α-DIO-hM4D(Gi)-mCherry-WPRE-pA |
|
Control |
PT-0013 rAAV-Ef1α-DIO-mCherry-WPRE-pA
PT-0012 rAAV-DIO-eYFP-WPRE-pA |
Tingting Sun, Zihua Song, Yanghua Tian, Wenbo Tian, Chunyan Zhu, Gongjun Ji, Yudan Luo, Shi Chen, Likui Wang, Yu Maoa, Wen Xie, Hui Zhong, Fei Zhao, Min-Hua Luo, Wenjuan Tao, Haitao Wang, Jie Li, Juan Li, Jiangning Zhou, Kai Wang, and Zhi Zhang
Pub Date: 2019-02-11,
DOI: 10.1073/pnas.1814292116，
Email: [email protected]
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.
Fig. 1 BLAGlu neurons preferentially synapse on mPFCGABA.
The pathophysiology underlying obsessive-compulsive disorder (OCD) remains unclear, leading to major challenges in the treatment of OCD patients. Using viral neuronal tracing in mice, the authors define a critical BLA
Glu→mPFC
GABA→Glu circuit through which compulsive checking behavior is generated. A mechanistic functional understating of this circuit will provide insight into the possible mechanisms underlying human OCD checking symptoms.
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