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A Disinhibitory Microcircuit Mediates Conditioned Social Fear
hChR2-mCherry (From BrainVTA) was used for optogenetic manipulation. hM3D(Gq)-mCherry and hM4D(Gi)-mCherry were used for pharmacogenetic inactivation or inhibition of dmPFC principal neurons. AAV-GCaMP6m was used to measure activities of dmPFC SST neurons with fiber photometry.
The viruses used in this article from BrainVTA are in the table below
Optogenetic PT-0002 AAV2/9-EF1a-double floxed-hChR2 (H134R)-mCherry
Haifeng Xu, Ling Liu, Yuanyuan Tian, JunWang, Jie Li, Junqiang Zheng, Hongfei Zhao, Miao He, Tian-Le Xu, Shumin Duan, and Han Xu
Pub Date: 2019-03-18,  DOI: 10.1016/j.neuron.2019.02.026, Email:
Fear behavior is under tight control of the prefrontal cortex, but the underlying microcircuit mechanism remains elusive. In particular, it is unclear how distinct subtypes of inhibitory interneurons (INs) within prefrontal cortex interact and contribute to fear expression. We employed a social fear conditioning paradigm and induced robust social fear in mice. We found that social fear is characterized by activation of dorsalmedial prefrontal cortex (dmPFC) and is largely diminished by dmPFC inactivation. With a combination of in vivo electrophysiological recordings and fiber photometry together with cell-type-specific pharmacogenetics, we further demonstrated that somatostatin (SST) INs suppressed parvalbumin (PV) INs and disinhibited pyramidal cells and consequently enhanced dmPFC output to mediate social fear responses. These results reveal a previously unknown disinhibitory microcircuit in prefrontal cortex through interactions between IN subtypes and suggest that SST INs-mediated disinhibition represents an important circuit mechanism in gating social fear behavior.
Figure 1. Effect of Pharmacogenetic Inactivation of dmPFC Pyramidal Cells on Social Fear
Prefrontal cortex plays an essential role in fear expression. Xu et al. reveal a disinhibitory microcircuit in prefrontal cortex through interactions between interneuron subtypes and suggest that SST INs-mediated disinhibition represents an important circuit mechanism in gating social fear behavior.
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