The ability to detect conspecific＇s distress is crucial for animal survival. In rodent models, observational fear （OF） occurs when one animal perceives another fear related negative emotions, which may model certai...The ability to detect conspecific＇s distress is crucial for animal survival. In rodent models, observational fear （OF） occurs when one animal perceives another fear related negative emotions, which may model certain behaviors caused by witnessing traumatic experiences in humans. Anterior cingulate cortex （ACC） has been showed to play a crucial role in OF. However, cellular and neural circuit basis relating to ACC governing OF is poorly understood. Here, we used Designer Receptor Exclusively Activated by a Designer Drug （DREADD） system to investigate the cell type specific circuit mechanism of ACC in OF. Firstly, inhibitory hM4D （Gi） designer receptor together with clozapine N-oxide （CNO） injection was applied to inactivate ACC neurons in the observer mice. We found that, chemogenetic inhibition of ACC resulted in a decreased freezing response in the observer mice. Next, combining PV-ires-Cre mice and Cre-dependent DREADD system, we selectively targeted the ACC parvalbumin （PV） interneurons with the excitatory hM3D （Gq） designer receptor. Activation of ACC PV interneurons following CNO injection reduced freezing response in the observer mice, while had no effect on freezing response in the demon- strator mice. Finally, monosynaptic rabies retrograde tracing revealed that ACC PV interneurons receive inputs from the mediodorsal thalamic nucleus （MD） and the ventromedial thalamic nucleus （VM）, both known for their roles in OF. Taken together, these findings reveal that ACC activation is important for OF, during which PV interneurons in ACC play an important regulatory role. Abnormal function of ACC PV interneurons might contribute to the pathology of empathy- deficits related diseases, such as autism and schizoohrenia.展开更多
基金supported by Shanghai Municipal Science and Technology Major Project(No.2018SHZDZX01)Shanghai Center for Brain Science and Brain-Inspired Technology。
基金partially sponsored by the National Natural Science Foundation of China(NSFC 81425010(L.W.),31630031(L.W.),31500861(Z.Z.),31471109(L.L.)International Partnership Program of Chinese Academy of Sciences,172644KYS820170004(L.W.)+5 种基金External Cooperation Program of the Chinese Academy of Sciences,GJHZ1508(L.W.)Guangdong Provincial Key Laboratory of Brain Connectome and Behavior,2017B030301017(L.W.)Shenzhen Governmental Grants,JCYJ20150529143500959(L.W.),JCYJ20150401150223647(Z.Z.),JCYJ20151030140325151(L.L)Shenzhen Governmental grants KQJSCX20160301144002(L.L.)Shenzhen Discipline Construction Project for Neurobiology DRCSM[2016]1379(L.W.)Ten Thousand Talent Program(L.W.)
文摘The ability to detect conspecific＇s distress is crucial for animal survival. In rodent models, observational fear （OF） occurs when one animal perceives another fear related negative emotions, which may model certain behaviors caused by witnessing traumatic experiences in humans. Anterior cingulate cortex （ACC） has been showed to play a crucial role in OF. However, cellular and neural circuit basis relating to ACC governing OF is poorly understood. Here, we used Designer Receptor Exclusively Activated by a Designer Drug （DREADD） system to investigate the cell type specific circuit mechanism of ACC in OF. Firstly, inhibitory hM4D （Gi） designer receptor together with clozapine N-oxide （CNO） injection was applied to inactivate ACC neurons in the observer mice. We found that, chemogenetic inhibition of ACC resulted in a decreased freezing response in the observer mice. Next, combining PV-ires-Cre mice and Cre-dependent DREADD system, we selectively targeted the ACC parvalbumin （PV） interneurons with the excitatory hM3D （Gq） designer receptor. Activation of ACC PV interneurons following CNO injection reduced freezing response in the observer mice, while had no effect on freezing response in the demon- strator mice. Finally, monosynaptic rabies retrograde tracing revealed that ACC PV interneurons receive inputs from the mediodorsal thalamic nucleus （MD） and the ventromedial thalamic nucleus （VM）, both known for their roles in OF. Taken together, these findings reveal that ACC activation is important for OF, during which PV interneurons in ACC play an important regulatory role. Abnormal function of ACC PV interneurons might contribute to the pathology of empathy- deficits related diseases, such as autism and schizoohrenia.
