Tweaking neurons in lab animals could help reveal what makes us individuals
Kay Tye, 36
Here are some of the things Kay Tye relishes: break dancing, rock-climbing, snowboarding, poker, raising her young daughter and son. These adrenaline-fueled activities all require basic skills. But true mastery — and the joy Tye finds in them — comes from improvisation. She boldly steps into a void, a realm where she has to riff, and trusts that a flash of insight will lead the way out.
As a 36-year-old neuroscientist studying how the brain creates experiences, Tye brings this mix of fearlessness and creativity to her lab, where it’s a key ingredient to her success. “Kay always finds this interesting twist,” says Leslie Vosshall, a molecular neurobiologist at Rockefeller University in New York City. Tye’s group at MIT investigates scientific questions in innovative ways, often with powerful results.
The goal, Tye says, is ambitious: to identify — in neuroscientific terms — the core of what makes us individuals. We all live in the same world, but have vastly different experiences of it. Our private emotions and motivations are crucial for driving our behavior. But just how our inner mental lives are created, she says, is a mystery: “How do we actually ground the mind in the brain?”
So far, Tye’s findings — which come in large part from tweaking nerve cells, and behaviors, in lab animals — have led to a deeper understanding of the intricate neural forces that shape experiences. Many of those forces may operate similarly in people, she believes.
One insight came unexpectedly. After a series of experiments on how certain nerve cells respond to cocaine, the data were in shambles. But Tye and postdoctoral researcher Gillian Matthews didn’t shy from the project. Instead, they ventured into the void, hunting for inventive ways to explain the puzzling results.
It turns out that these nerve cells, buried in a part of the mouse brain called the dorsal raphe nucleus, weren’t responding to cocaine at all. They were reacting to a mouse version of loneliness.
In the course of the experiments, some of the mice were isolated. In mice reintroduced to companions after a period of solitude, dorsal raphe nerve cells grew very active, Tye and colleagues reported in 2016 in Cell. Using a technique called optogenetics, developed in Karl Deisseroth’s lab at Stanford, where Tye was a postdoc, the researchers turned these same cells on artificially with a laser.
Though the mice didn’t seem to like the sensation, avoiding a place where the stimulation happened, the artificial kick made the mice more social. Tye suspects that these cells play a role in creating a sensation similar to loneliness or alleviating it by promoting social interactions. The results in mice offer a handhold to explore how these nerve cells might work together to create the mind.
“We threw away what we originally thought, completely,” Tye says. “The word cocaine doesn’t appear in the paper. It was really fun to go on that journey with [Matthews], because where we ended up was not where we thought we were going to go.”
In another experiment using optogenetics, Tye and colleagues pitted the sensations of reward and punishment against each other in rats. Published in the June Nature Neuroscience, the results describe the neural pathways that help an animal decide whether to risk a shock for a sweet treat. Looking at reward and punishment simultaneously in this way is not something other researchers had done.
These insights into motivated behaviors come from blending state-of-the-art techniques with clever experimental design, says neuroscientist Joseph LeDoux of New York University. The question of how the brain decides on a behavior is a classic one, and Tye is “taking it to a new level of neurobiological sophistication,” he says.
It takes my breath away quite frequently to see someone blossom and grow and develop and get stronger and get more capable and more confident.
— Kay Tye
But she’s not doing it alone. At MIT, where Tye also did her undergraduate work before going to the University of California, San Francisco for a Ph.D., she heads a research lab full of people Vosshall describes as “fiercely loyal and incredibly hardworking.”
Helping her graduate students find their scientific footing is one of Tye’s favorite parts of the job, a task she likens to the dynamic role of being a mother to young children. “It takes my breath away quite frequently,” Tye says, “to see someone blossom and grow and develop and get stronger and get more capable and more confident.”
The joy Tye finds in nurturing her science tribe is obvious and no doubt provides opportunities to go off script. In science and in her personal life, she delights in the unexpected, an inclination evident from her poker game. Some poker players “grind it out,” playing a “very careful, tight game,” she says. “That’s not the way I enjoy playing. The hands I like being in the most are where anything can happen.”
G.A. Matthews et al. Dorsal raphe dopamine neurons represent the experience of social isolation. Cell. Vol. 164, February 11, 2016, p. 617. doi: 10.1016/j.cell.2015.12.040.
A. Burgos-Robles et al. Amygdala inputs to prefrontal cortex guide behavior amid conflicting cues of reward and punishment. Nature Neuroscience. Vol. 20, June 2017, p. 824. doi: 10.1038/nn.4553.
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