A Substantia Innominata-midbrain Circuit Controls a General Aggressive Response

Abstract

SUMMARYAnimals display various aggressive behaviors essential for survival, while ‘uncontrollable’ attacks and abnormal aggressive states have massive social costs. Neural circuits regulating specific forms of aggression under defined conditions have been described, but whether there are circuits governing a general aggressive state to promote diverse aggressive behaviors remains unknown. Here, we found that posterior substantia innominata (pSI) neurons responded to multiple aggression-provoking cues with 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 state, the pSI-PAG circuit universally drives multiple aggressive behaviors and thus may provide a potential target for alleviating human pathological aggression.

Neural dynamics in the limbic system during male social behaviors

“…We selected 13 brain regions that have either been implicated in aggressive and/or sexual behaviors or are strongly connected with those regions for Ca 2+ recording during social behaviors. The list includes five hypothalamic regions -medial preoptic nucleus (MPN), anterior hypothalamic nucleus (AHN), ventrolateral part of the ventromedial hypothalamus (VMHvl), dorsomedial hypothalamus (DMH) and ventral premammillary nucleus (PMv), five amygdala regions -anterior medial amygdala (MeAa), posterodorsal medial amygdala (MeApd), posterior amygdala (PA), posteromedial cortical amygdala (CoApm) and posteromedial bed nucleus of stria terminalis (BNSTpm), and three regions outside of amygdala and hypothalamus -ventral part of lateral septum (LSv), ventral subiculum (SUBv) and lateral periaqueductal gray (lPAG) (Figure 1A) (Bayless et al, 2019;Chang and Gean, 2019;Chen et al, 2020;Falkner et al, 2020;Hong et al, 2014;Karigo et al, 2020;Lee et al, 2014;Lenschow and Lima, 2020;Leroy et al, 2018;Lin et al, 2011;Lischinsky and Lin, 2020;Newman, 1999;Stagkourakis et al, 2020;Stagkourakis et al, 2018;Unger et al, 2015;Wei et al, 2018;Wong et al, 2016;Xie et al, 2020;Yamaguchi et al, 2020;Yang et al, 2013;Yang et al, 2017;Zelikowsky et al, 2018;Zha et al, 2020;Zhu et al, 2020). Each of these 13 regions is densely connected with multiple other recorded regions and expresses abundant Esr1, with the exceptions of AHN, LSv, and PAG, where Esr1 expression is modest.…”

An approximate line attractor in the hypothalamus that encodes an aggressive internal state

“…The same method could also distinguish low-vs. high-intensity aggressive behavior (i.e., dominance mount vs. attack) at well above chance accuracy (67.3%± 2.9%, N=3 mice). Perhaps due to the slow dynamics of activity along this dimension, behaviors occurring close together in time, such as attack and sniff-attack (defined as periods of sniffing that occurred within one second prior to attack, as described by (Zhu et al, 2020)) could not be distinguished using this dimension. Remarkably, none of the other eight fit dimensions could be used to distinguish aggressive behaviors from sniffing with above chance accuracy (Figure 2F, G; Supplemental Figure S2C).…”