Aubry Antonio V, Durand-de Cuttoli Romain, Karpman Elizabeth, Fisher-Foye Rachel L, Parise Lyonna F, Cathomas Flurin, Burnett C Joseph, Yang Yewon, Yuan Chongzhen, LaBanca Alexa R, Chan Kenny L, Winston Kion T, Lin Hsiao-Yun, Dackour Farah, Tavallaei Arman A, Alvarez Johana, Nishioka Tadaaki, Morishita Hirofumi, Froemke Robert C, Li Long, Russo Scott J
Nash Family Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Brain and Body Research Center and Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.
Nature. 2025 Mar;639(8056):1006-1015. doi: 10.1038/s41586-024-08540-4. Epub 2025 Feb 12.
Aggression is an evolutionarily conserved behaviour that controls social hierarchies and protects valuable resources. In mice, aggressive behaviour can be broken down into an appetitive phase, which involves approach and investigation, and a consummatory phase, which involves biting, kicking and wrestling. Here, by performing an unsupervised weighted correlation network analysis on whole-brain FOS expression in mice, we identify a cluster of brain regions, including hypothalamic and amygdalar subregions and olfactory cortical regions, that are highly co-activated in male but not in female aggressors. The posterolateral cortical amygdala (COApl)-an extended olfactory structure-was found to be a hub region, on the basis of the number and strength of correlations with other regions in the cluster. Our data also show that oestrogen receptor 1 (Esr1)-expressing cells in the COApl (COApl) exhibit increased activity during attack behaviour and during bouts of investigation that precede an attack, in male mice only. Chemogenetic or optogenetic inhibition of COApl cells in male aggressors reduces aggression and increases pro-social investigation without affecting social reward and reinforcement behaviour. We further show that COApl projections to the ventromedial hypothalamus and central amygdala are necessary for these behaviours. Collectively, these data suggest that, in aggressive males, COApl cells respond specifically to social stimuli, thereby enhancing their salience and promoting attack behaviour.
攻击行为是一种进化上保守的行为,它控制着社会等级制度并保护宝贵资源。在小鼠中,攻击行为可分为两个阶段:一个是欲望阶段,包括接近和探究;另一个是完成阶段,包括撕咬、踢打和扭打。在这里,通过对小鼠全脑FOS表达进行无监督加权相关网络分析,我们确定了一组脑区,包括下丘脑和杏仁核亚区以及嗅觉皮质区,这些脑区在雄性而非雌性攻击者中高度共激活。基于与该簇中其他区域相关性的数量和强度,发现后外侧皮质杏仁核(COApl)——一种扩展的嗅觉结构——是一个枢纽区域。我们的数据还表明,仅在雄性小鼠中,COApl中表达雌激素受体1(Esr1)的细胞在攻击行为期间以及攻击前的探究阶段表现出活性增加。对雄性攻击者的COApl细胞进行化学遗传或光遗传抑制可减少攻击行为并增加亲社会探究,而不影响社会奖励和强化行为。我们进一步表明,COApl向腹内侧下丘脑和中央杏仁核的投射对于这些行为是必要的。总体而言,这些数据表明,在具有攻击性的雄性中,COApl细胞对社会刺激有特异性反应,从而增强其显著性并促进攻击行为。