Stress controllability modulates basal activity of dopamine neurons in the substantia nigra compacta.

Prolonged stress induces neural maladaptations in mesolimbic dopamine (DA) system and produces emotional and behavioral disorders. However, the effects of stress on activity of DA neurons are diverse and complex that hinge on the type, duration, intensity, and controllability of stressors. Here, controlling the duration, intensity, and type of the stressors to be identical, we observed effects of stressor controllability on the activity of substantia nigra compacta (SNc) DA neurons in mice. We found that both lack and loss of control over shock enhance the basal activity and intrinsic excitability of SNc DA neurons via modulation of Ih current, but not via corticosterone serum level. Moreover, loss of control over shock produces more significant enhancement in the basal activity of SNc DA neurons than that produced shock per se, and therefore attenuates the response to natural reward. This attenuation can be reversed by control over shock. These results indicate that although chronic stress per se tends to enhance the basal activity of SNc DA neurons, loss of control over the stressor is able to induce a larger enhancement in basal activity of SNc DA neurons and produce more severe behavioral deficits. However, control over stress ameliorates the deleterious effects of stress, highlighting the role of stress controllability.Significance statementThe impact of stress on the DA system significantly modifies immediate and guide future behaviors. Stress does not have unitary effects on VTA DA neurons, but the effects of stress controllability on SNc DA neurons are unclear. The present work studied the effects of controllability on the activity of SNc DA neurons by controlling the duration, intensity, and pattern of footshocks to be identical. The results show that loss of control over shock produces larger enhancement in basal activity of SNc DA neurons and worse behavioral deficits than what caused by uncontrollable shock per se. The results demonstrate the critical role of stress controllability in modulating activity of SNc DA neurons and inducing behavioral deficits.