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A retinoraphe projection regulates serotonergic activity and
AAVs of tracing helper and RV were used for retrograde monosynaptic tracing. AAV-GCaMP6m was used for fiber photometry. AAV-ChR2 and AAV-eNpHR3.0 were used for optogenetic manipulation. AAV-hM3D and AAV-hM4D were used for chemogenetics manipulation. (From BrainVTA)
The viruses used in this article are in the table below
Tracing Helper  AAV-EF1a-DIO-EGFP-TVA
 AAV-EF1a-DIO-RVG
 rAAV-hSyn-GFP-2a-TVA-2a-RVG-WPRE-pA
Calcium sensors  AAV-DIO-GCaMP6m
Optogenetic  AAV-DIO-ChR2-mCherry
 AAV-DIO-eNpHR3.0-mCherry
Chemogenetics  AAV-DIO-hM3D-mCherry
 AAV-DIO-hM4D-mCherry
Control  AAV-DIO-Eyfp
 AAV-DIO-mCherry
RV  SAD-DG-DsRed (EnvA)
Lu Huang, Tifei Yuan, Minjie Tan, Yue Xi, Yu Hu, Qian Tao, Zhikai Zhao, Jiajun Zheng, Yushui Han, Fuqiang Xu, Minmin Luo, Patricia J. Sollars, Mingliang Pu, Gary E. Pickard, Kwok-Fai So, Chaoran Ren
Pub Date: 2017-03-31, DOI: 10.1038/ncomms14908, Email: [email protected]
Animals promote their survival by avoiding rapidly approaching objects that indicate threats. In mice, looming-evoked defensive responses are triggered by the superior colliculus (SC) which receives direct retinal inputs. However, the specific neural circuits that begin in the retina and mediate this important behaviour remain unclear. Here we identify a subset of retinal ganglion cells (RGCs) that controls mouse looming-evoked defensive responses through axonal collaterals to the dorsal raphe nucleus (DRN) and SC. Looming signals transmitted by DRN-projecting RGCs activate DRN GABAergic neurons that in turn inhibit serotoninergic neurons. Moreover, activation of DRN serotoninergic neurons reduces looming-evoked defensive behaviours. Thus, a dedicated population of RGCs signals rapidly approaching visual threats and their input to the DRN controls a serotonergic self-gating mechanism that regulates innate defensive responses. Our study provides new insights into how the DRN and SC work in concert to extract and translate visual threats into defensive behavioural responses.

Figure 1. DRN-projecting RGCs are necessary for looming-induced c-Fos activation of SC-LP-BLA pathway.
This study is aimed to explore the specific neural circuits that begin in the retina and mediate looming-evoked defensive responses. By combining conventional neurotracer, transneuronal rabies virus tracing techniques and an array of brain circuit interrogation tools, including immunotoxin-based RGC ablation, c-Fos activity mapping, fibre photometry, chemogenetics and optogenetics, the authors report that DRN/SC-projecting RGCs are necessary for looming-induced defensive responses and that DRN 5-HT neuron activity regulates the circuits that control looming-evoked behaviour.
 
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