In the News

As an NIH New Innovator, Kay Tye Takes on Obesity
October 01, 2013
Photo Credit: Najat Kessler

Assistant professor of neuroscience Kay M Tye has studied the brain circuits underlying addiction, anxiety and depression, all major problems to the health of individuals and society. Now she wants to apply her training and the innovative techniques she has developed to obesity. “Obesity is linked to the neural circuitry of the other behaviors but it may be the most pressing problem because it is the most prevalent and it is increasing,” she says. “Our currently available treatments for obesity are ineffective and completely insufficient for the problem that faces our society.”

So Tye proposed a strategy to discover the neural circuits underlying obesity and then reprogram them to eliminate obsessive craving and consumption. The proposal was bold, creative and risky – just the kind of high-stakes project the NIH seeks to support with the Director’s New Innovator Award. Her gamble paid off. Tye has been named a New Innovator for 2013 and will receive $1.5 million over the course of five years. The award is designed specifically to support unusually creative new investigators with highly innovative research ideas at an early stage of their career when they may lack the preliminary data required for traditional funding mechanisms.

“It’s a huge honor to be recognized as a new innovator by this amazing NIH program and to be associated with all the other people who have won the award this year and in the past. Now I have a chance to make my vision a reality and to make a dramatic difference in obesity research.”

Tye joined the Picower Institute in January 2012 and by August 2013 published a paper in Neuron reporting the discovery of minute sub-circuits among the two well-studied brain regions involved in anxiety, the basolateral amygdala and the ventral hippocampus, based on work conducted in her new lab. Her obesity project will build on the methods she used to drill down to unprecedented detail in the circuitry and also her graduate school training with animal models of addiction, which she conducted at University of California, San Francisco.

Sugar Addiction

Addiction is thought to “hijack” the brain’s natural reward system that motivates us to seek food and other necessities for survival. Because sugar is an inherently powerful natural reward – in nature, it was scarce and signaled a desirable high-energy food – many addiction protocols use a sucrose solution to study an animal’s reward-seeking behavior. But, research recently suggests, sugar can also hijack the brain’s reward system, and can also rewire the brain so that cues – a cookie at the cash register – can fire a craving that drives behavior.
“We plan to use the brain’s natural plasticity, the ability to rewire itself, to reprogram the reward system so that sugar cues no longer trigger the transition from craving to compulsive consumption,” Tye explains. However, the reprogramming must be precise and specific to excessive sugar consumption so that it does not reduce overall appetite for healthy food or for seeking other natural rewards.

Sub-circuit Projections

To avoid that pitfall, Tye will adapt the optogenetic technology she has been refining since her postdoctoral training in Karl Deisseroth’s lab at Stanford University. In optogenetics, researchers modify neurons to express a light-activated protein and then use brief pulses of light to instantly activate or inhibit the specific type of neuron carrying the protein in a living animal. The researcher can then control a small subset of neurons that are intermingled among other neural types in a discrete brain region such as the amygdala, which is implicated in anxiety. But within that subset, smaller subsets can connect to different brain regions, producing different functions when activated. Tye’s innovation was to activate not the neurons’ cell bodies in their home region but rather their axon terminals in the different regions they project to. Using that method in her recent paper, “We found a novel circuit underlying anxiety, a distinct projection that has completely different effects on anxious behavior than you see when you nonspecifically activate the entire amygdala and get an average of all responses.”

Reprogramming Craving

Now she will apply this technique to the natural reward circuit involved in sugar craving and obesity in animal models. Among the technologies she foresees her lab applying to this problem is a wireless implanted device that can simultaneously record from the sub-circuits involved in craving-compulsion-consumption while also optogentically stimulating or inhibiting them to define their discrete functions. Also simultaneously, machine-learning algorithms under development in her lab will decode the neural signature that predicts craving, compulsion and consumption. When the algorithm identifies a “craving” signal in real time, the device will instantly but briefly inhibit the precise neural activity underlying craving, which, if successful, will prevent the over-consumption of sugar. Her lab will also explore non-invasive means of controlling the craving, such as ultrasound or transcranial magnetic stimulation.
How, then, will this achievement be translated to humans to help stop the obesity epidemic? Perhaps instead of going in for gastric bypass surgery or liposuction, a person will go to a type of biofeedback lab for training to restore the brain’s normal wiring in the reward circuit. Ultimately, those are engineering problems and, she notes, MIT is the right place to solve them. “You have to take a big risk to make a big change.”