Dopamine neurons modulate neural encoding and expression of depression-related behavior. This study investigates the causal role of dopamine neurons in depression-like behaviors induced by chronic mild stress (CMS) in freely moving rodents. Using behavioral, pharmacological, optogenetic, and electrophysiological methods, the researchers found that bidirectional control of midbrain dopamine neurons modulates multiple depression symptoms. Optogenetic activation of these neurons alters the neural encoding of depression-related behaviors in the nucleus accumbens (NAc), suggesting that processes affecting depression symptoms involve changes in the neural encoding of action in limbic circuits. The study shows that selective inhibition of ventral tegmental area (VTA) dopamine neurons acutely induces depression-like behaviors, while phasic activation reverses these behaviors. Chronic mild stress induces a lasting depression-like phenotype, which can be reversed by phasic activation of VTA dopamine neurons. The NAc dopamine receptors are essential for the action of these neurons in depression-related escape behavior. The study also demonstrates that NAc neurons encode phasic activation of VTA dopamine neurons and depression-related escape behavior. The findings suggest that dopamine neurons play a causal role in both the induction and relief of depression-related behaviors. The study highlights the importance of understanding the neural circuits underlying depression and the potential for targeted interventions. The results provide insights into the complex interactions between stress, dopamine systems, and depression-related behaviors. The study also emphasizes the need for further research to understand the heterogeneity of mood disorders and the precise neural mechanisms involved in depression.Dopamine neurons modulate neural encoding and expression of depression-related behavior. This study investigates the causal role of dopamine neurons in depression-like behaviors induced by chronic mild stress (CMS) in freely moving rodents. Using behavioral, pharmacological, optogenetic, and electrophysiological methods, the researchers found that bidirectional control of midbrain dopamine neurons modulates multiple depression symptoms. Optogenetic activation of these neurons alters the neural encoding of depression-related behaviors in the nucleus accumbens (NAc), suggesting that processes affecting depression symptoms involve changes in the neural encoding of action in limbic circuits. The study shows that selective inhibition of ventral tegmental area (VTA) dopamine neurons acutely induces depression-like behaviors, while phasic activation reverses these behaviors. Chronic mild stress induces a lasting depression-like phenotype, which can be reversed by phasic activation of VTA dopamine neurons. The NAc dopamine receptors are essential for the action of these neurons in depression-related escape behavior. The study also demonstrates that NAc neurons encode phasic activation of VTA dopamine neurons and depression-related escape behavior. The findings suggest that dopamine neurons play a causal role in both the induction and relief of depression-related behaviors. The study highlights the importance of understanding the neural circuits underlying depression and the potential for targeted interventions. The results provide insights into the complex interactions between stress, dopamine systems, and depression-related behaviors. The study also emphasizes the need for further research to understand the heterogeneity of mood disorders and the precise neural mechanisms involved in depression.