Mice exposed to social defeat stress can be separated into those that are susceptible to the paradigm's depressive effects, and those that are resilient. The authors found that susceptible mice exhibited hyperactivity of ventral tegmental area dopamine (VTA DA) neurons that was linked to a pathological upregulation of the hyperpolarization-activated current Ih. Surprisingly, resilient mice showed an even greater increase in Ih but maintained normal VTA DA neuron activity through homeostatic plasticity mechanisms. Experimentally increasing Ih or VTA DA neuron activity had an antidepressant effect in susceptible mice, suggesting that boosting the brain's natural resilience mechanisms may aid the treatment of depression.