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Activation of the dopaminergic pathway from VTA to the medial
AAV-hChR2 and AAV- eNpHR3.0 were used for optogenetic manipulation. AAV-hM4Di was used for chemogenetics manipulation. AAV-Gcamp6s was used for calcium-dependent fiber photometry. (All the viruses are from BrainVTA)
The viruses used from BrainVTA in this article are in the table below
 Optogenetic  AAV9-EF1a-floxed-ChR2-mCherry
Chemogenetics  AAV9-EF1a-floxed-hM4Di-mCherry
Calcium sensors  AAV9-hsyn-Gcamp6s
Control  AAV9-EF1a-floxed-mCherry
Zhijian Zhang, Qing Liu, Pengjie Wen, Jiaozhen Zhang, Xiaoping Rao, Ziming Zhou, Hongruo Zhang, Xiaobin He, Juan Li, Zheng Zhou, Xiaoran Xu, Xueyi Zhang, Rui Luo, Guanghui Lv, Haohong Li, Pei Cao, Liping Wang, Fuqiang Xu
Pub Date: 2017-12-18, DOI: 10.7554/elife.25423, Email:
Odor-preferences are usually influenced by life experiences. However, the neural circuit mechanisms remain unclear. The medial olfactory tubercle (mOT) is involved in both reward and olfaction, whereas the ventral tegmental area (VTA) dopaminergic (DAergic) neurons are considered to be engaged in reward and motivation. Here, we found that the VTA (DAergic)-mOT pathway could be activated by different types of naturalistic rewards as well as odors in DAT-cre mice. Optogenetic activation of the VTA-mOT DAergic fibers was able to elicit preferences for space, location and neutral odor, while pharmacological blockade of the dopamine receptors in the mOT fully prevented the odor-preference formation. Furthermore, inactivation of the mOT-projecting VTA DAergic neurons eliminated the previously formed odor-preference and strongly affected the Go-no go learning efficiency. In summary, our results revealed that the VTA (DAergic)-mOT pathway mediates a variety of naturalistic reward processes and different types of preferences including odor-preference in mice.

Figure 1. Inputs of the mOT.
This study is aimed to explore the neural circuit mechanisms underlying the olfactory and reward systems. Using virus-based tracing system, fiber photometry recording, optogenetic and chemogenetics manipulation, the results demonstrate that activation of the VTA (DAergic)-mOT pathway generates odor-preference as well as the other types of preferences. Thus, this pathway might be a key player in modulating perception of a given stimulus.
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