Functional identification of an aggression locus in the mouse hypothalamus.
Lin Dayu,Boyle Maureen P,Dollar Piotr,Lee Hyosang,Lein E S,Perona Pietro,Anderson David J
Electrical stimulation of certain hypothalamic regions in cats and rodents can elicit attack behaviour, but the exact location of relevant cells within these regions, their requirement for naturally occurring aggression and their relationship to mating circuits have not been clear. Genetic methods for neural circuit manipulation in mice provide a potentially powerful approach to this problem, but brain-stimulation-evoked aggression has never been demonstrated in this species. Here we show that optogenetic, but not electrical, stimulation of neurons in the ventromedial hypothalamus, ventrolateral subdivision (VMHvl) causes male mice to attack both females and inanimate objects, as well as males. Pharmacogenetic silencing of VMHvl reversibly inhibits inter-male aggression. Immediate early gene analysis and single unit recordings from VMHvl during social interactions reveal overlapping but distinct neuronal subpopulations involved in fighting and mating. Neurons activated during attack are inhibited during mating, suggesting a potential neural substrate for competition between these opponent social behaviours.
A substantia innominata-midbrain circuit controls a general aggressive response.
Zhu Zhenggang,Ma Qingqing,Miao Lu,Yang Hongbin,Pan Lina,Li Kaiyuan,Zeng Ling-Hui,Zhang Xiaoxing,Wu Jintao,Hao Sijia,Lin Shen,Ma Xiulin,Mai Weihao,Feng Xiang,Hao Yizhe,Sun Li,Duan Shumin,Yu Yan-Qin
Although aggressive behaviors are universal and essential for survival, "uncontrollable" and abnormal aggressive behaviors in animals or humans may have severe adverse consequences or social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but how brain circuits govern a general aggressive response remains unknown. Here, we found that posterior substantia innominata (pSI) neurons responded to several aggression-provoking cues with the graded activity of differential dynamics, predicting the aggressive state and the topography of aggression in mice. Activation of pSI neurons projecting to the periaqueductal gray (PAG) increased aggressive arousal and robustly initiated/promoted all the types of aggressive behavior examined in an activity-level-dependent manner. Inactivation of the pSI circuit largely blocked diverse aggressive behaviors but not mating. By encoding a general aggressive response, the pSI-PAG circuit universally drives multiple aggressive behaviors and may provide a potential target for alleviating human pathological aggression.
Mechanically evoked defensive attack is controlled by GABAergic neurons in the anterior hypothalamic nucleus.
Innate defensive behaviors triggered by environmental threats are important for animal survival. Among these behaviors, defensive attack toward threatening stimuli (for example, predators) is often the last line of defense. How the brain regulates defensive attack remains poorly understood. Here we show that noxious mechanical force in an inescapable context is a key stimulus for triggering defensive attack in laboratory mice. Mechanically evoked defensive attacks were abrogated by photoinhibition of vGAT neurons in the anterior hypothalamic nucleus (AHN). The vGAT AHN neurons encoded the intensity of mechanical force and were innervated by brain areas relevant to pain and attack. Activation of these neurons triggered biting attacks toward a predator while suppressing ongoing behaviors. The projection from vGAT AHN neurons to the periaqueductal gray might be one AHN pathway participating in mechanically evoked defensive attack. Together, these data reveal that vGAT AHN neurons encode noxious mechanical stimuli and regulate defensive attack in mice.