Behavioural and dopaminergic signatures of resilience

Chronic stress can have lasting adverse consequences in some individuals, yet others are resilient to the same stressor(1,2). Susceptible and resilient individuals exhibit differences in the intrinsic properties of mesolimbic dopamine (DA) neurons after the stressful experience is over(3,)(8). However, the causal links between DA, behaviour during stress and individual differences in resilience are unknown. Here we recorded behaviour in mice simultaneously with DA neuron activity in projections to the nucleus accumbens (NAc) (which signals reward(9,12)) and the tail striatum (TS) (which signalsthreat(13,16)) during social defeat. Supervised and unsupervised behavioural quantification revealed that during stress, resilient and susceptible mice use different behavioural strategies and have distinct activity patterns in DA terminals in the NAc (but not the TS). Neurally, resilient mice have greater activity near the aggressor, including at the onset of fighting back. Conversely, susceptible mice have greater activity at the offset of attacks and onset of fleeing. We also performed optogenetic stimulation of NAc-projecting DA neurons in open loop (randomly timed) during defeat or timed to specific behaviours using real-time behavioural classification. Both open-loop and fighting-back-timed activation promoted resilience and reorganized behaviour during defeat towards resilience-associated patterns. Together, these data provide a link between DA neural activity, resilience and resilience-associated behaviour during the experience of stress.

Automated summary

This research reveals differences in DA neuron activity and behavior between resilient and susceptible individuals after experiencing stress. Resilient mice show more activity near the aggressor, while susceptible mice exhibit more activity at the end of attacks and the beginning of fleeing. Optogenetic stimulation of NAc-projecting DA neurons can promote resilience and alter behavior during defeat.