A research team that includes five current and former NARSAD Young Investigator Grantees has made an important contribution to our growing understanding of how the brain shapes decisions about when and how much we eat. These findings may have important implications for the treatment of eating disorders.
Nandakumar S. Narayanan, M.D., Ph.D., of the University of Iowa, a 2012 NARSAD Young Investigator Grantee, has been studying how the neurotransmitter dopamine influences a part of the brain called the prefrontal cortex (PFC). The PFC plays a vital role in cognition and decision-making. Although Dr. Narayanan is ultimately interested in developing new approaches to treating schizophrenia—an illness in which function of the PFC is affected—in work published January 19th online in Nature Neuroscience, he and colleagues report discovery of a role for dopamine in the regulation of food intake.
Specifically, the researchers looked at neurons in the PFC that have receptors, or docking ports, for one of several variants of the dopamine molecule. Neurons with these particular receptors, called D1 receptors, are widespread in the PFC, and prior research has shown they have various associations with both hunger and the perception of food in humans. Animal studies have been inconclusive, however, in helping establish more detailed knowledge.
Dr. Narayanan used a technique pioneered by co-author Karl Deisseroth, M.D., Ph.D., of Stanford University—a 2005 NARSAD Young Investigator Grantee and current member of the Foundation’s Scientific Council—to stimulate D1 neurons in the PFC of mice with color beams of laser light. This revealed that feeding increased when the neurons were stimulated and that the affected PFC neurons were part of a circuit that connected with a portion of the amygdala, another part of the brain that is involved in the regulation of memory, emotion and behavior.
To the researchers’ surprise, feeding could be increased in the animals simply by stimulating the connecting axons in the amygdala, rather than solely at their source in D1 neurons in the PFC. Axons are nerve fibers that project from a neuron to transmit electrical impulses from the neuron to other neurons, muscles and glands.
Thus, in addition to their previously known roles in the PFC, D1 neurons in the PFC are now understood to be directly involved in the feeding response, a function that appears to be regulated via interaction with the amygdala. “This circuit presents new therapeutic opportunities, as future interventions for obesity or eating disorders may consider this prefrontal circuit” as a target for new drugs, the team writes.
Other former NARSAD Young Investigator Grantees who contributed to the research, all of Yale University, are: Maysa Sarhan, Ph.D. (2009); Douglas J. Guarnieri, Ph.D. (2010); and Ralph J DiLeone, Ph.D. (2002, 2004).