It’s that time of year again: holiday parties and family feasts! One of the most frequently made—and most often broken—New Year’s resolutions is to follow a sensible diet. All goes well until you catch sight of a cupcake or smell some cookies fresh out of the oven. Sensory cues trigger cravings that crumble resolve and, before you know it, you’re on a sugar high.
Actually, from a biological perspective, it’s not a fair fight. Once desires and preferences are hard-wired in the brain, people have difficulty changing their habits. But one of 2013 recipients of the NIH Director’s New Innovator Award, Kay Tye of the Massachusetts Institute of Technology (MIT), Cambridge, MA, is up for the challenge. In a high-risk, high-reward research project, she’s trying to find ways to control food cravings by reprogramming the brain, where the behavior begins.
Tye says her interest in the human brain began when she was a freshman at MIT and met H.M.—perhaps the most iconic patient in the history of brain research. H.M. was intriguing because experimental brain surgery had left him unable to form new memories, yet the old ones remained intact—a sign that there are multiple memory systems at work in the human brain. From that point on, she knew she wanted to study neuroscience, specifically memory. She began with emotional memories, including those associated with food, images, and songs. But what intrigued her the most was how emotional memories could affect health and disease.
As a graduate student, she studied addiction and neural activity underlying addictive behaviors, which are motivated by the brain’s reward system. Her thesis focused on understanding the brain activity that linked a positive cue (think of a TV commercial or fast-food sign) with the delivery of a sugary drink. Tye discovered there were specific neurons in brain regions called the amgydala and the ventral tegmental area that together seem to orchestrate sugar-seeking behavior [1,2,3,4,5]. She also explored the neural processes that triggered a relapse in sugar-seeking behaviors.
During her postdoctoral fellowship, she learned cutting-edge techniques that allowed her to control the activity of specific neurons and circuits in rodents. She found that she could essentially turn off the brain’s sugar-seeking circuits using a new neuromodulation tool called optogenetics, which uses light in combination with light-sensitive reagents. The result? When the circuits were altered, the rodents’ preference for sugar solution over water was greatly reduced .
After joining the faculty at MIT, she took her research one step further and began to ask whether it might be possible to treat or prevent obesity in animals by reprogramming circuits in the brain. The brain’s reward system—which evolved when food was scarce and calories had to be consumed and stored—encourages the consumption of sugary treats with a pleasurable blast of the neurotransmitter dopamine (think about how you feel after eating your favorite food). While this reward pathway may have been a good motivator when our ancestors hunted and gathered for survival, this hard-wired reward system can be harmful to our health in today’s calorie-rich environment.
If Tye succeeds in curbing sugar-seeking in animals by permanently reprogramming brain circuits with optogenetics, then her next goal is to develop and test drugs or other non-invasive methods to target these craving circuits. If that’s successful, the final step will be to test such therapies in humans.
But we all know that biomedical progress, even that generated by high-risk, high-reward efforts, doesn’t happen overnight. So, while Tye and other researchers work to figure out if it’s possible to develop therapies to reprogram sugar-seeking behaviors, it looks like you’ll just have to rely on old-fashioned willpower to steer clear of the goodies.
This blog is going to be taking a brief holiday break, but I’ll be back in a couple of weeks with more news from the frontiers of NIH-funded science. Until then, Happy Holidays and warm wishes for the New Year to all!
 Amygdala neurons differentially encode motivation and reinforcement. Tye KM, Janak PH. J Neurosci. 2007 Apr 11;27(15):3937-45.
 Rapid strengthening of thalamo-amygdala synapses mediates cue-reward learning. Tye KM, Stuber GD, de Ridder B, Bonci A, Janak PH. Nature. 2008 Jun 26;453(7199):1253-7.
 Amygdala neural encoding of the absence of reward during extinction. Tye KM, Cone JJ, Schairer WW, Janak PH. J Neurosci. 2010 Jan 6;30(1):116-25.
 Methylphenidate facilitates learning-induced amygdala plasticity. Tye KM, Tye LD, Cone JJ, Hekkelman EF, Janak PH, Bonci A. Nat Neurosci. 2010 Apr;13(4):475-81.
 Dopamine neurons modulate neural encoding and expression of depression-related behaviour. Tye KM, Mirzabekov JJ, Warden MR, Ferenczi EA, Tsai HC, Finkelstein J, Kim SY, Adhikari A, Thompson KR, Andalman AS, Gunaydin LA, Witten IB, Deisseroth K. Nature. 2013 Jan 24;493(7433):537-41.
High-Risk, High-Reward Research. (NIH Common Fund)
Kay M. Tye, A Novel Strategy for Combating Obesity: Reprogramming Neural Circuits , Massachusetts Institute of Technology
The Tye Laboratory, MIT
NIH Funding: National Institute on Drug Abuse