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Substance P in the medial amygdala regulates aggressive behaviors in male mice

Neuropsychopharmacology (2024)Cite this article

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Abstract

Behavioral and clinical studies have revealed a critical role of substance P (SP) in aggression; however, the neural circuit mechanisms underlying SP and aggression remain elusive. Here, we show that tachykinin-expressing neurons in the medial amygdala (MeATac1 neurons) are activated during aggressive behaviors in male mice. We identified MeATac1 neurons as a key mediator of aggression and found that MeATac1→ventrolateral part of the ventromedial hypothalamic nucleus (VMHvl) projections are critical to the regulation of aggression. Moreover, SP/neurokinin-1 receptor (NK-1R) signaling in the VMHvl modulates aggressive behaviors in male mice. SP/NK-1R signaling regulates aggression by influencing glutamate transmission in neurons in the VMHvl. In summary, these findings place SP as a key node in aggression circuits.

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Fig. 1: Ca2+ activity of MeATac1 neurons during aggressive and non-social behaviors.
Fig. 2: MeATac1 neurons mediate aggressive behaviors in male mice.
Fig. 3: MeATac1→VMHvl projections regulate aggressive behaviors in male mice.
Fig. 4: SP/NK1-R signaling regulates aggression.
Fig. 5: SP potentiates excitatory transmission in the VMHvl.

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Data availability

The data that support the findings of this study are available on request from the corresponding author upon reasonable request.

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Funding

This work was supported by the STI 2030—Major Projects 2021ZD0204000 (2021ZD0204003) and the National Natural Science Foundation of China (32071018).

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  1. These authors contributed equally: Mei-Hui Yue, Kai-Jie Liu.

Authors and Affiliations

  1. Key Laboratory of Molecular Epigenetics Ministry of Education, Institute of Genetics and Cytology, Northeast Normal University, Changchun, 130021, China

    Zi-Xuan He, Mei-Hui Yue, Kai-Jie Liu, Yao Wang, Jiu-Ye Qiao, Xin-Yue Lv, Ke Xi, Ya-Xin Zhang, Jia-Ni Fan, Hua-Li Yu, Xiao-Xiao He & Xiao-Juan Zhu

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Contributions

ZXH designed and conducted all the experiments; KJL and MHY carried out the calcium imaging, behavioral tests and immunohistochemistry work; YW, KX, JYQ, XYL and KJL conducted the virus experiments; JNF, YXZ, XXH and HLY helped collect the data; ZXH and XJZ cowrote the article; ZXH and XJZ supervised all aspects of the project.

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Correspondence to Xiao-Juan Zhu.

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He, ZX., Yue, MH., Liu, KJ. et al. Substance P in the medial amygdala regulates aggressive behaviors in male mice. Neuropsychopharmacol. (2024). https://doi.org/10.1038/s41386-024-01863-w

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