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Anterior Cingulate Cortex to Ventral Hippocampus Circuit Medi
AAV- hM3Dq (From BrainVTA) and AAV-hM4Di were used for chemogenetic manipulations to specifically evaluate the contribution of ACC, dHPC and vHPC neurons in contextual fear discrimination. AAV- EGFP (From BrainVTA)  was used for retrograde tracing to test the projection relationship between the ACC and vHPC.
The viruses used in this article from BrainVTA are in the table below
Chemogenetics  PT-0049 AAV9-CaMKIIα-hM3Dq-mCherry
Control  PT-0241 rAAV2/R-hSyn-EGFP-WPRE-pA
Pub Date: 2019-07-17,  DOI: 10.1523/JNEUROSCI.2739-18.2019Email: [email protected]
Xin-Lan Bian, Cheng Qin, Cheng-Yun Cai, Ying Zhou, Yan Tao, Yu-Hui Lin, Hai-YinWu, Lei Chang, XChun-Xia Luo and Dong-Ya Zhu
Contextual fear memory becomes less context-specific over time, a phenomenon referred to as contextual fear generalization. Overgen-eralization of contextual fear memory is a core symptom of post-traumatic stress disorder (PTSD), but circuit mechanisms underlying the generalization remain unclear. We show here that neural projections from the anterior cingulate cortex (ACC) to ventral hippocampus (vHPC) mediate contextual fear generalization in male mice. Retrieval of contextual fear in a novel context at a remote time point activated cells in the ACC and vHPC, as indicated by significantly increased C-fos + cells. Using chemogenetic or photogenetic manipulations, we observed that silencing the activity of ACC or vHPC neurons reduced contextual fear generalization at the remote time point, whereas stimulating the activity of ACC or vHPC neurons facilitated contextual fear generalization at a recent time point. We found that ACC neurons projected to the vHPC unidirectionally, and importantly, silencing the activity of projection fibers from the ACC to vHPC inhibited contextual fear generalization at the remote time point. Together, our findings reveal an ACC to vHPC circuit that controls expression of fear generalization and may offer new strategies to prevent or reverse contextual fear generalization in subjects with anxiety disorders, especially in PTSD.

Fig1. Projection pattern between the ACC and dHPC.
To reveal the circuit mechanisms of contextual fear memory, the authors used chemogenetic (From BrainVTA) or photogenetic manipulations to study. Finally, the study indicates that neural projections from the anterior cingulate cortex to ventral hippocampus control the expression of contextual fear generalization. Thus, manipulating the circuit may prevent or reverse fear overgeneralization in subjects with PTSD.
 
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