Neural circuits for coping with social defeat

Abstract

When resources, such as food, territory, and potential mates are limited, competition among animals of the same species is inevitable. Over bouts of agonistic interactions, winners and losers are determined. Losing is a traumatic experience, both physically and psychologically. Losers not only need to deploy a set of species-specific defensive behaviors to minimize the physical damage during defeat, but also adjust their behavior towards the winners to avoid future fights in which they are likely disadvantaged. The expression of defensive behaviors and the fast and long-lasting changes in behaviors accompanying defeat must be supported by a complex neural circuit. This review summarizes the brain regions that have been implicated in coping with social defeat, one centered on basolateral amygdala and the other on ventromedial hypothalamus. Gaps in our knowledge and hypotheses that may help guide future experiments are also discussed.

Figure 1:. Mouse behavior during defeat, followed by social and contextual avoidance.

During an aggressor encounter, the aggressor will attack and bite the opponent, prompting escape and defensive behaviors including dashing, pushing, jumping, freezing, and assuming an upright posture. Post encounter, the defeated mouse avoids contact with the aggressor (trace represents mouse movement, notice confinement to corners and edges) and contexts associated with the defeat experience. The defeated mouse is shown in light gray and the aggressor is shown in dark gray.

Figure 2:. Neural circuitry involved in fear conditioning and social defeat learning.

Blue highlights regions with potential roles in Pavlovian fear conditioning. Red indicates regions relevant for coping with social defeat, including social defense, defeat induced social avoidance, and defeat induced contextual avoidance. Shade indicates the strength of the supporting evidence. Brighter color corresponds to stronger evidence. Abbreviations: lateral septum (LS), medial prefrontal cortex (mPFC), nucleus accumbens (NAc), ventral hippocampus (vHipp), central amygdala (CeA), basolateral amygdala (BLA), medial amygdala (MeA), ventrolateral part of the ventromedial hypothalamus (VMHvl), lateral hypothalamic area (LHA), dorsal part of the premammillary nucleus (PMd) and bed nucleus of the stria terminalis (BNST).

Figure 3:. Defeat learning hypothesis at the VMHvl.

Prior to defeat, conspecific cues preferentially activate posterior VMHvl, eliciting approach and attack. During defeat, anterior VMHvl cells are activated by painful bites, driving defensive behaviors. Repeated pairing of pain during defeat and multimodal inputs from the aggressor leads to potentiation of synapses carrying aggressor cues. Consequently, aggressor cues become sufficient to preferentially drive avoidance behaviors in future aggressor encounters. The test mouse is shown in light gray.