Anhedonia, or the inability to feel pleasure or enjoyment, is a key symptom in several mental illnesses including major depression and schizophrenia. This sense of pleasure is generated in part by the brain’s neural pathways involved in seeking and experiencing reward. In a new study by led by Karl Deisseroth, M.D., Ph.D., of Stanford University, researchers have now identified in rodents some of the neural circuitry that appears to regulate reward behavior across different sections of the brain.

By controlling the activity of dopamine neurons in a part of the brain called the medial prefrontal cortex, Deisseroth, a Scientific Council member and 2005 and 2007 Young Investigator, and his colleagues reported in the January 1 issue of Science that they can produce symptoms of anhedonia in rodents. Hyperactivity in the medial prefrontal cortex in humans has been associated with anhedonia in patients with depression. In rats, stimulating activity in that part of the brain caused the animals to avoid their preferred sugar water and shy away from socializing with their cage-mates.

The scientists used a combination of functional magnetic resonance imaging and optogenetics (a technique that uses pulses of light to control specific brain cells) to observe how the activity in the reward circuitry in the medial prefrontal cortex can suppress activity in other parts of the brain, such as the striatum, that are involved in reward-seeking behavior. Together, these findings provide a much clearer picture of how reward-seeking pathways operate in the brain, and may help scientists learn more about how these pathways relate to anhedonia.

Deisseroth was joined on the study by Conor Liston, M.D., Ph.D., a 2013 Young Investigator at Weill Cornell Medical College; Melissa R. Warden, Ph.D., a 2012 Young Investigator at Cornell University; Amit Etkin, M.D., Ph.D., a 2012 Young Investigator, and Brian Knutson, Ph.D., a 2003 Young Investigator, both at Stanford University. Doctoral students Emily Ferenczi and Kelly Zalocusky, both of the Deisseroth lab, were co-first authors of the paper along with Dr. Liston.

Takeaway: New experiments in rodents trace out the brain circuitry involved in anhedonia, the inability to experience pleasure that is an important symptom of major depression and schizophrenia.