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Direct auditory cortical input to the lateral periaqueductal
RV-DsRed was used for retrograde monosynaptic tracing,hChR2 and eNpHR3.0 viruses were used for optogenetic manipulation. hM4D(Gi) viruses were used for chemogenetic manipulations, Cre-dependent AAV was used to visualize collateral pathways. (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
Chemogenetic  PT-0043 rAAV-Ef1α-DIO-hM4D(Gi)-mCherry-WPRE-pA
Control  PT-0013 rAAV-Ef1α-DIO-mCherry-WPRE-pA
Pub Date: 2019-09-19, DOI: 10.1371/journal.pbio.3000417 Email:
HaitaoWang, Jiahui Chen, Xiaotong Xu,Wen-Jian Sun, Xi Chen, Fei Zhao, Min-Hua Luo, Chunhua Liu, Yiping Guo,Wen Xie, Hui Zhong, Tongjian Bai,Yanghua Tian, Yu Mao1,, Chonghuan Ye,Wenjuan Tao, Jie Li, Zahra FarzinpourID,Juan Li, Jiang-Ning Zhou, KaiWang, Jufang He, Lin Chen, Zhi Zhang
Threatening sounds can elicit a series of defensive behavioral reactions in animals for survival, but the underlying neural substrates are not fully understood. Here, we demonstrate a previously unexplored neural pathway in mice that projects directly from the auditory cortex(ACx) to the lateral periaqueductal gray (lPAG) and controls noise-evoked defensive behaviors. Electrophysiological recordings showed that the lPAG could be excited by a loud noise that induced an escape-like behavior. Trans-synaptic viral tracing showed that a great number of glutamatergic neurons, rather than GABAergic neurons, in the lPAG were directly innervated by those in layer V of the ACx. Activation of this pathway by optogenetic manipulations produced a behavior in mice that mimicked the noise-evoked escape, whereas inhibition of the pathway reduced this behavior. Therefore, our newly identified descending pathway is a novel neural substrate for noise-evoked escape and is involved in controlling the threat-related behavior.

Fig.1 Using viral tracing strategies to dissect a neural pathway that mediates sound-induced defense behavior.
To reveal specific brain regions involved in the noise-elicited escape behavior, RV-DsRed viruses (From BrainVTA) were used for retrograde tracing and AAV viruses (From BrainVTA) were used for optogenetic and chemogenetic manipulations. This study identifies a novel and cell type–specific glutamatergic (Glu)ACx→GlulPAG projection that controls noise-evoked escape.
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