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Resilience is mediated by beneficial adaptations in the face of adversity,such as prolonged stress.However,in contrast to stress-induced pathological alterations,neural circuit adaptations for resilience remain largely unknown.In a well-established social defeat stress model of depression,we found that locus coeruleus norepinephrine neurons projecting to the ventral tegmental area(VTA)exhibit enhanced firing activity selectively in resilient mice.Optogenetically mimicking this firing adaptation in previously defined susceptible mice reverses their depressionrelated behaviors.Circuit-and cell type-specific molecular profiling studies reveal that α1 and β3 adrenergic receptors are highly expressed in VTA dopamine neurons projecting to the nucleus accumbens,and pharmacologically activating these receptors induces similar pro-resilient effects.These findings elucidate a norepinephrine circuit as a resilience pathway in the brain,and provide new molecular targets for therapeutically promoting resilience.