Figure 1.
Noradrenergic hyperactivity establishes homeostasis in mesolimbic dopamine neurons to maintain or promote resilience to social stress. Following repeated social defeat stress, mice are segregated into susceptible (depressed) or resilient (non-depressed) sub-populations. Within the resilient group, homeostasis is established by an intrinsic balance of excitatory Ih and inhibitory K+ currents to maintain control-like firing activity in VTA DA neurons that project to the NAc. This current study further expands on this finding by demonstrating that the resilient group exhibits an increase in firing activity of LC neurons that project to the VTA. Repeated optogenetic stimulation induced hyperactivity of the LC-VTA circuit and was sufficient to promote the resilient phenotype in previously defined susceptible mice by re-establishing the aforementioned homeostatic balance in mesolimbic DA neurons. Reversing susceptibility to promote resilience was mediated by VTA α1 and β3 adrenergic receptors.