Neuroscience has often focused on dividing the brain into regions, pinpointing which individual neurons are responsible for specific functions. Kay Tye’s vision of the brain is defined less by discrete addresses than by the roads between them—the connections between groups of neurons. “I think neuroscience as a field is at this threshold of a new understanding of the brain in terms of circuits,” says Tye, a principal investigator at the Picower Institute for Learning and Memory at MIT. The connections a cell makes could be at least as important as its location, she believes.

As a postdoc at Stanford University, Tye took advantage of a relatively new technology called optogenetics, which allows researchers to use light to turn specific, genetically modified neurons on and off in lab animals. 

Manipulating the connections in mice between a group of neurons in the amygdala with a group in the hippocampus, she precisely altered behaviors related to both anxiety and social interaction to tease apart the specific connections she suspected played a critical role in anxiety. When the circuit is inhibited, a mouse that normally avoids open areas explores them freely, and when it’s activated, the mouse runs for cover. In a subsequent study, Tye showed that inhibiting a circuit made a mouse sniff and nudge a strange mouse in its cage, while activating it made the mouse ignore the stranger—a test of the animal’s tendency toward social interaction. 

The idea that manipulating connections between small bundles of brain cells could instantly reshape behavior opens up new possibilities for treating brain disorders. Current drugs, she says, “target the entire body and bathe the whole brain in this soup,” creating many unwanted side effects. If scientists can find a way to safely manipulate the human neural connections involved in feelings such as anxiety, therapies might be more precise and cause fewer side effects. 

First, researchers will have to identify the various connections that can be manipulated this way. It’s an enormous task given the complexity of the brain. But at least Tye’s breakthroughs have helped get them on the right road. 

—Courtney Humphries

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