Mount Sinai researchers have discovered different roles for two dopamine receptors located in nerve cells within the portion of the brain that controls the approach to avoidance behavior. These receptors potentially influence anxiety and mood disorders whose origins are not yet clear.
The team characterized the function of dopamine and D2 receptors in the ventral mice hippocampus, a region involved in the regulation of emotions and responses to stress. His work expands the knowledge of the field of dopamine signaling beyond his known actions in other brain regions that influence reward and motivation, and prepares the scenario for future research on dopamine deregulation in a variety of anxiety and depressive disorders. The study results appeared in the May 7 edition of Nature.
“The healthy and deregulated emotional emotional processing related to the ability of an individual to resolve conflicts between the approach and the avoidance when making decisions at the moment has involved the hippocampus,” says the principal author Eric J. Nestler, MD, PHD, professor of the Nash Family of Neuroscience and director of the Friedman brain institute of the Icahn School of Medicine Sinaai, and director of Sinai Health System. “Ours is the first complete functional study of the cells that express D1 and D2 in the ventral hippocampus. We demonstrate that dopamine is more important in that area of the brain than was previously believed and, in addition, that transmits information related to decision making in stressful conditions.”
The hippocampus coordinates decision making in inductive situations of anxiety, such as when an individual has to choose whether to obtain food or drinks under threatening situations. Such focus/avoidance dilemmas, where a particular objective has desirable and potentially undesirable consequences, can cause excessive fear, confusion and anxiety in humans.
The Mount Sinai team investigated the influence of dopamine signaling within the ventral hippocampus on approximation/avoidance behavior in male mice. The researchers learned that Dopamine D1 and D2 receptors expressed in different neuronal populations are called to play to help execute focus/avoidance decisions. These receptors and the cells that express them mediate the opposite approach/avoidance responses, and are differentially affected by the transmission of dopamine in that region of the brain.
The team was surprised to know that the neuronal cells that express D1 and D2 receptors, which are more enriched in the striated body, a critical part of the motor and reward system, are also relevant in the hippocampus. Another unexpected behavioral observation was that mice whose D2 cells were artificially activated much less fearful.
“These discoveries stressed for us that dopamine is an important component of the hippocampus circuits and that the signage of dopamine must be reconsidered in many brain regions where it was previously overlooked, especially those associated with learning, memory and emotional behavior,” says Dr. Nestler, whose considerable research over the years has been designed to better understand the molecular mechanisms of drugs and Depression “Our work further implies the deregulation of dopamine in anxiety and mood disorders.”
Dr. Nestler attributes to the two co-first of the authors of the study, Arthur Godino, PHD, graduated student and then postdoctoral fellow, and Marine Salery, PHD, postdoctoral member and the rest of the great research team for the creative advances carried out in this research.
The next step for Dr. Nestler and his team is to show precisely how the dopamine hippocampus circuit that modulates the approach/avoidance is deregulated in several stress -related conditions, such as anxiety disorders and major depressive disorders (which imply greater avoidance) and drug addiction (where people seek drug rewards despite the harmful consequences).
“By helping to delineate the neuromodulatory circuits that govern these disorders,” says Dr. Nestler, “we are taking an essential step to address a main cause of disability in humans around the world.”
This work was funded by subsidies from the National Institute of Drug Abuse, National Institute of Mental Health and the Hope For Depression Research Foundation.