“Together, obesity and Type 2 diabetes rank among our nation’s greatest health problem, and they largely result from what many call an “addiction” to sugar. But solving this problem is more complicated than solving drug addiction, because it requires reducing the drive to eat unhealthy foods without affecting the desire to eat healthy foods when hungry. In a new paper in Cell, neuroscientists at MIT have untangled these two processes in mice and shown that inhibiting a previously unknown brain circuit that regulates compulsive sugar consumption does not interfere with healthy eating. “For the first time, we have identified how the brain encodes compulsive sugar seeking and we’ve also shown that it appears to be distinct from normal, adaptive eating,” says senior author Kay Tye, a principle investigator at the Picower Institute for Learning and Memory who previously developed novel techniques for studying brain circuitry in addiction and anxiety. “We need to study this circuit in more depth, but our ultimate goal is to develop safe, noninvasive approaches to avert maladaptive eating behaviors, first in mice and eventually in people.” Drug addiction is defined as compulsive drug-seeking despite adverse consequences at school, work, or home. Addictive drugs “hijack” the brain’s the natural reward-processing center, the ventral tegmental area (VTA). But food is a natural reward and, unlike a drug, is necessary for survival, so it has been unclear whether overeating results from a similar compulsion, or from something else. “This study represents, in my opinion, an outstanding step forward in understanding the many intricate aspects of feeding behaviors,” says Antonello Bonci, scientific director at the National Institute on Drug Abuse, who was not involved with the research. “While there have been many excellent studies in the past, looking at the compulsive drive of substance-use disorders, this is the first time that a study goes very deeply and comprehensively into the same aspects for compulsive feeding behavior. From a translational perspective, the extraordinary multidisciplinary approach used in this study produced a very exciting finding: that compulsive sugar consumption is mediated by a different neural circuit than physiological, healthy eating. For the study, Tye and her graduate student Edward Nieh focused on the connections between the VTA and the lateral hypothalamus (LH), which controls feeding. But because the LH also controls diverse other behaviors and connects to multiple other brain regions, no one had yet isolated a feeding and reward-processing circuit. Tye and Nieh first identified and characterized just the LH neurons that connect to the VTA and recorded their naturally occurring activities in brain slices, with the help of Gillian Matthews, before moving to animal experiments. Electrodes recorded the activity of these identified neurons during animal behaviors.”

• Decoding Neural Circuits that Control Compulsive Sucrose Seeking