Abstract
A common phenomenon called social buffering (SB), communication within conspecific animals is a benefit for a stressed individual to better recover from aversive events, is crucial to all mammals. Although the dopamine reward system has been implicated in SB, it is not clear which neuronal populations are relevant and how they contribute. Here, we adopted a learned helplessness (LH) animal model of depression and found that LH subjects housed with a conspecific partner show better performance in the shuttle box test, showing that SB improves the stress-coping abilities to deal with stress. Bidirectional manipulation of ventral tegmental area (VTA) dopamine neurons by chemogenetic tools can mimic or block the SB effect in LH mice. To screen for SB-induced structure plasticity of VTA dopamine neurons, we employed viral genetic tools for mapping input and output architecture and found LH- and SB-triggered circuit-level changes in neuronal ensembles. Zona incerta (ZI), an overlapping brain region, was significantly changed in both anterograde and retrograde tracing during LH and SB. These results reveal a neural loop with structural plasticity between VTA dopamine neurons and ZI underlies the SB effects in LH and lays a foundation for studying how VTA dopamine neurons regulate SB-related neural circuits.
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Acknowledgements
We appreciated Qian Zhang and Feng He for their technical assistant.
Funding
This work was supported financially by grants from the National Natural Science Foundation of China (No. 31571044, 31871073 to B.T., and No. 31600821 to P.Z.), Program for New Century Excellent Talents in University (No. NCET- 10–0415 to B.T.), and the Fundamental Research Funds for the Central Universities (HUST: 2019kfyXJJS081 to P.Z.).
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This study was designed by Bo Tian, Jie Ming, Pei Zhang, and Hongwei Cai. The experiments were complemented by Hongwei Cai, Guangjian Qi, Lijun Zhang, Ming Li, Xinyuan Lv, and Jie Lei. Statistical analysis was performed by Hongwei Cai and Tongxia Li. Hongwei Cai and Pei Zhang finished manuscript writing. Bo Tian, Jie Ming, and Pei Zhang provide the supervision and final check.
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Cai, H., Zhang, P., Qi, G. et al. Systematic Input–Output Mapping Reveals Structural Plasticity of VTA Dopamine Neurons-Zona Incerta Loop Underlying the Social Buffering Effects in Learned Helplessness. Mol Neurobiol 59, 856–871 (2022). https://doi.org/10.1007/s12035-021-02614-4
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DOI: https://doi.org/10.1007/s12035-021-02614-4