Tiago Branco Unveils How the Brain Computes Behavior

For years, Tiago Branco, a neuroscientist at University College London (UCL) Sainsbury Wellcome Center, has been fascinated by how the brain works. As a postdoctoral researcher at the laboratory of UCL neuroscientist Michael Häusser, he focused on how neurons process the information they receive. Branco showed that single dendrites can differentiate inputs from other neurons and that different parts of a neuron seem to process distinct types of information.^1,2

Branco’s research on single neurons caught The Scientist’s attention, and we featured his work in 2012. To celebrate our 40^th anniversary, we reached out to him again to see how his quest to understand the brain’s inner workings has progressed. In the past decade, Branco’s research moved from single neurons to whole neuronal circuits that determine and guide escape decisions in mice—a body of work that expands what neuroscientists know of how the brain implements behaviors that are essential for survival.

To Escape or Not to Escape

Animals must survive to pass on their genes to the next generation. The brain is fine-tuned to implement behaviors that ensure survival, and escape behavior is one such. To effectively avoid harm, animals must first detect a threat, then initiate their escape, execute the behavior, and finally end their escape once they find a safe location.³

To Branco, escape is an interesting behavior to study because it has a very well-defined starting point, and researchers can easily control the characteristics of a threatening stimulus, such as its intensity, which helps them map the behavior to the animal’s brain activity.

An image that shows brain cells in blue and pink. — Neurons (in blue) in the brain’s periaqueductal gray control the escape response of mice when they face a threat.
Dominic Evans and Vanessa Stempel

In one of Branco’s team’s early studies, the researchers set out to determine how animals decide whether to escape or not—a decision that relies on the brain reaching a certain threshold before triggering the behavioral response, Branco said. By changing the intensity of a threatening stimulus, the researchers found that the neuronal connection between two brain structures known to play a role in escaping, namely the medial superior colliculus and the dorsal periaqueductal gray, sets the threshold for deciding when to initiate escape.⁴ An interesting feature of this connection, Branco added, is that it is weak.

“[This] means that if the threat intensity is not very high, the escape neurons never get activated. It's only when you start having a lot of activity, that you recruit enough neurons to go through this connection and activate the escape neurons,” he said.

Choosing a Path to Safety

While investigating the neural underpinnings of the escape response, Branco also became intrigued by how animals compute routes to safety. His team first showed that mice escape to a previous shelter location when faced with a threat for a second time, suggesting that the animals memorize where the shelter is and use that information to guide future escapes.⁵ In real-life scenarios, animals often have multiple possible escape routes, and Branco’s team sought to investigate how animals decide which path to take when they have different route options to choose from.

The researchers used the fabrication laboratory at their institution to build a set of experimental platforms. These had paths with arms of different lengths and angles in relation to the animal’s starting point, or the team could dynamically flip the platform’s configuration to make a particular route unavailable at specific time points during the experiment. Mice exposed to a threatening visual or auditory stimulus often chose the shortest path to shelter, which they learned as they explored the environment.⁶

“That’s really important because learning by trial and error when the consequence of getting it wrong is to be killed, it's not a good thing,” Branco explained. “That's why mice and many other species can learn about things like where safety is and what paths to safety are just through exploration, without having been exposed to the threat.”

As his team continues to drill down into how the brain implements escape behavior, Branco plans to expand his research into other organisms, including other mouse species and even crabs, to uncover fundamental principles that different animals may share. He also hopes to explore how specific genes contribute to setting an animal’s threat sensitivity by studying a mouse species that is “super chill” and comparing the responses of these animals to other mice when faced with potentially harmful stimuli.

A Mentor, a Science Explorer

After more than a decade as a group leader, Branco is grateful for creating a work environment that produces quality science and fosters interpersonal bonds that make working in his lab an enjoyable and enriching experience—an achievement that reveals how much he values being a mentor. “We’re training PhD students and postdocs, and you have a responsibility to contribute to the education and the development of these people as much as possible,” said Branco, adding that this entails not just helping them become group leaders but preparing them to be successful in whatever they want to do.

Reflecting on his career, Branco feels privileged to have worked at institutions that allowed him to explore scientific paths without fearing failure along the way. “With limited funding, for a limited period of time, you can only do so much, no matter how dedicated and good you are,” Branco said. “Having the luxury of being able to say, ‘You know what? I don't care if this project takes four or five years,’ that allows you to do more comprehensive science.”

In Branco’s eyes, this scientific freedom contributed to his transition from single neurons to brain circuits and behavior and allowed him to produce quality science in the field, for which he is content. “We're understanding a bit better how the brain implements escape,” he said. “Looking back and saying, ‘Okay, I think I contributed some knowledge to our understanding of this particular problem in neuroscience,’ that, as a scientist, is as much as you can hope for, right?”

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