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Neural circuit mechanisms that govern inter-male attack in mice

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Abstract

Individuals of many species fight with conspecifics to gain access to or defend critical resources essential for survival and reproduction. Such intraspecific fighting is evolutionarily selected for in a species-, sex-, and environment-dependent manner when the value of resources secured exceeds the cost of fighting. One such example is males fighting for chances to mate with females. Recent advances in new tools open up ways to dissect the detailed neural circuit mechanisms that govern intraspecific, particularly inter-male, aggression in the model organism Mus musculus (house mouse). By targeting and functional manipulating genetically defined populations of neurons and their projections, these studies reveal a core neural circuit that controls the display of reactive male–male attacks in mice, from sensory detection to decision making and action selection. Here, we summarize these critical results. We then describe various modulatory inputs that route into the core circuit to afford state-dependent and top–down modulation of inter-male attacks. While reviewing these exciting developments, we note that how the inter-male attack circuit converges or diverges with neural circuits that mediate other forms of social interactions remain not fully understood. Finally, we emphasize the importance of combining circuit, pharmacological, and genetic analysis when studying the neural control of aggression in the future.

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Fig. 1
Fig. 2

Modified from Lo et al. [94]. Brain regions that account for > 2% of the total inputs to or outputs of the VMHvlEsr1+ neurons are depicted. The size of the arrows indicates the relative connection strength, and the direction of the arrow indicates input to or output from the VMHvl. The color schemes are assigned based on the relative strength of the input and output connection from each brain region with the VMHvl. For brain regions that provide more inputs to than receive outputs from VMHvlEsr1+ neurons, if the normalized input value divided by the normalized output value (input/output) is > 4, they are colored red; and if the value is > 2 but < 4, these regions are colored orange. Similarly, for brain regions that receive more outputs from than send inputs to VMHvlEsr1+ neurons, if the normalized output value divided by the normalized input value (output/input) is > 4, they are colored dark blue; and if the value is > 2 but < 4, these regions are colored light green. All other connected brain regions with comparable input and output values are colored gray. ARC, arcuate hypothalamic nucleus; AHN, anterior hypothalamic nucleus; AVPV, anteroventral periventricular nucleus; BNST, bed nuclei of the stria terminalis; CEA, central amygdala nucleus; DMH, dorsomedial nucleus of the hypothalamus; LS, lateral septum; MeA, medial amygdala; mPOA, medial preoptic area; PA, posterior amygdala; PAG, periaqueductal gray; PB, parabrachial nucleus; PMv, ventral premammillary nucleus; PVN, paraventricular hypothalamic nucleus; PVT, paraventricular thalamus; pSI, posterior substantia innominate; SPFp, subparafascicular nucleus, parvicellular part; SUBv, subiculum, ventral part; TTd, taenia tecta, dorsal part

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Acknowledgements

We thank members of the Xu lab for their comments on the manuscript. This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (grantXDB32000000), the Shanghai Municipal Science and Technology Major Project (grant no. 2018SHZDZX05), the National Nature Science Foundation of China (grant nos. 31871066 and 31922028), China Postdoctoral Science Foundation (Grant No. 2020TQ0333 and 2020M681416).

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Zha, X., Xu, XH. Neural circuit mechanisms that govern inter-male attack in mice. Cell. Mol. Life Sci. 78, 7289–7307 (2021). https://doi.org/10.1007/s00018-021-03956-x

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