Around 10% of people will, at some point in their lives, suffer from depression, a mood disorder characterized by long periods of sadness, loss of motivation, excessive fatigue and a lack of interest in once-pleasurable activities known as anhedonia. Brain imaging studies demonstrate that many of the brain regions responsible for normally regulating mood show disrupted function in depression, which can be reversed by antidepressant drugs or behavioral and cognitive therapy. Researchers have turned to animal models of chronic stress to learn more about the neurobiology of depression. Chronically stressed mice show some symptoms that are similar to those of depressed humans: high levels of anxiety, less social interaction and anhedonia. As in humans, chronic stress in mice can lead to altered plasticity in various mood-related brain regions, including the hippocampus, amygdala, nucleus accumbens and prefrontal cortex. These changes in plasticity can be reversed by some antidepressant drugs, including ketamine, which has rapid antidepressant effects in patients. In this animation, we explore the neural circuits affected in depression and illustrate the molecular and cellular changes thought to underlie the effects of chronic stress and its remediation by antidepressant drugs.