This study investigates the role of dopamine neurons in the modulation of depression-like behaviors. The researchers used a combination of behavioral, pharmacological, optogenetic, and electrophysiological methods to explore the effects of selective inhibition and activation of ventral tegmental area (VTA) dopamine neurons in freely moving rodents. They found that inhibiting VTA dopamine neurons induced multiple depression-like behaviors, including reduced motivation and anhedonia. Conversely, activating VTA dopamine neurons reversed these depression-like phenotypes. The study also revealed that the nucleus accumbens (NAc) plays a crucial role in mediating these effects, with dopamine receptor blockade in the NAc blocking the antidepressant-like effects of VTA dopamine neuron activation. Additionally, the researchers observed that optogenetic recruitment of VTA dopamine neurons altered the neural encoding of depression-related behaviors in the NAc, suggesting that changes in neural encoding may underlie the observed behavioral effects. These findings provide insights into the causal dynamics of depression-related behaviors and highlight the potential of targeting VTA dopamine neurons as a therapeutic approach for depression.This study investigates the role of dopamine neurons in the modulation of depression-like behaviors. The researchers used a combination of behavioral, pharmacological, optogenetic, and electrophysiological methods to explore the effects of selective inhibition and activation of ventral tegmental area (VTA) dopamine neurons in freely moving rodents. They found that inhibiting VTA dopamine neurons induced multiple depression-like behaviors, including reduced motivation and anhedonia. Conversely, activating VTA dopamine neurons reversed these depression-like phenotypes. The study also revealed that the nucleus accumbens (NAc) plays a crucial role in mediating these effects, with dopamine receptor blockade in the NAc blocking the antidepressant-like effects of VTA dopamine neuron activation. Additionally, the researchers observed that optogenetic recruitment of VTA dopamine neurons altered the neural encoding of depression-related behaviors in the NAc, suggesting that changes in neural encoding may underlie the observed behavioral effects. These findings provide insights into the causal dynamics of depression-related behaviors and highlight the potential of targeting VTA dopamine neurons as a therapeutic approach for depression.