Getting cravings out of your head
Kay Tye is Skyping from a hotel in Turks and Caicos, a sultry escape from her hometown of frigid Cambridge, Massachusetts. She speaks with a breathless, wide-eyed giddiness, and with her sunburned face and ponytail, she looks the part of stoked college student. You might see Tye with her 18-month-old daughter and think new mom, or maybe yoga teacher, and you'd be right on both counts.
We'll forgive you for not guessing she's an award-winning breakdancer — as well as a groundbreaking neuroscientist whose work could have major implications for human health.
For most of us, losing weight means ditching the doughnuts or hitting the treadmill. Tye thinks we've got it all wrong, that instead of focusing on what we put into our mouths, we should be looking at what happens in the brain. And if the 33-year-old assistant professor of neuroscience at MIT is right, weight loss could be the tip of an iceberg. Her community certainly seems confident. Named one of MIT Technology Review's 35 Innovators Under 35 last year, Tye is "really a rising star in this field," says Ming-Hu Han, a neuroscientist at Mount Sinai Hospital.
It all comes down to a concept called optogenetics. First described in 2005 by MIT neuroscientist Ed Boyden and Stanford University bioengineer Karl Deisseroth, who mentored Tye when she did a postdoc in his lab, optogenetics is a technique in which scientists use light to switch neurons on and off. Since then, researchers around the world have used it to trigger and suppress seizures and depression-, anxiety- and PTSD-like symptoms.
In person, Tye is a bundle of energy who talks so fast it's hard to keep up. Unlike most scientists, she steers mostly clear of jargon, chatting as breezily about optogenetics as she does about her days competing in Bay Area breakdance battles. But the ascent to science-world fame was more gradual than skyrocket. Growing up among the trees and waterfalls of Ithaca, New York, known for vegetarian food and gorges as much as for Cornell, fostered in Tye a wonder for biology. Her parents, both scientists at Cornell University who first met on a U.S.-bound boat from Hong Kong, encouraged her, and when it came time for college, she majored in brain and cognitive sciences at MIT. "I just find the brain very, very interesting," Tye gushes. "I have this subjective experience, and I feel that it's real, and how is it being represented in my brain biologically?"
But school burned her out and left her with a nagging worry. Was science her true calling, or had she been passively stumbling along, following the most obvious and (for Tye, if not for the rest of us) easiest path? After graduation, the young woman set off on a quest: backpacking in Australia to get clear on her goals and desires. For that year, she lived on a remote cattle farm, taught yoga and even began penning a novel, a longtime dream. But writing left her lonely; she missed the sense of community in science and how the field built on itself.
So she earned a Ph.D. in neuroscience at the University of California, San Francisco, which is when she published her thesis in Nature, describing stronger neuron firing in a brain region called the lateral amygdala in rats learning to link a cue with a reward. Tye was eager to venture beyond correlating neurons to behaviors and actually control them. She did a postdoc in Deisseroth's lab to master optogenetics techniques, and two years later, she returned to MIT as a faculty member.
Tye's lab has already plunged into untangling the neural circuits involved in social behavior, like reward-processing. Tye used optogenetics to control a circuit that had been linked to reward-processing and observed how mice behaved with sugar as a reward. When she switched the circuit on, they still sought sugar, even when full and even if it meant suffering a mild electric shock, like how compulsive overeaters stuff themselves despite knowing about heart disease and other risks. Switching the circuit off stopped only compulsive eating. Hungry mice still looked for food, suggesting that a therapy that tweaks this circuit wouldn't affect normal eating behaviors important for survival. Of course, sugar addiction isn't the only cause of obesity, but it's a major factor, Tye says.
Tye's group has also identified a circuit that controls anxiety-related behaviors. Turning it on made mice hesitant to explore their surroundings and wary of unfamiliar mice; turning it off emboldened them. Tye wants to continue working to understand the circuits underlying fundamental social behaviors, relevant to multiple psychiatric disorders. Rather than using traditional diagnoses like anxiety and depression, she envisions clinicians searching for disturbances in these circuits. This could all result in treatments that target specific individuals and specific problems, versus prescribing a drug that may or may not succeed — a drug that almost always has side effects.
To be sure, the full potential of Tye's work is far from fruition. "I think optogenetics has huge potential in helping to understand mental health and give us new avenues to treating mental health," says Sheena Josselyn, a neuroscientist at the University of Toronto, "but do I think we should take someone who has schizophrenia and put an implant in their brain right now? No." Josselyn doesn't see "a clear translation" to human studies. Tye herself notes that optogenetics probably won't appear in the clinic for several years. Plus, she's identified only a handful of neural circuits underlying reward-seeking and other social behaviors. Many more may underlie the same behaviors; an effective therapy might mean manipulating multiple circuits.
A vast network of circuits spans our most complex organ. Tye has just begun the unraveling. But her boundless curiosity and exuberance might be just what allows her to push forward. "It's just fun," she says, flashing a dimpled grin. "Really fun."
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