Scientists have gained new insight into how neurons in the brain communicate during a decision, and how connections between neurons can help reinforce a choice.

The study — conducted in mice and led by neuroscientists at Harvard Medical School — is the first to combine structural, functional and behavioral analyzes of how neuron-to-neuron connections support decision-making.

Results appear on February 21. The nature.

“How the brain is organized to help make decisions is a big, fundamental question, and the neural circuitry — how neurons are connected to each other — in the brain regions that are important for decision-making. , is not well understood,” said. Wei Ching-Allen Lee, associate professor of neurobiology at HMS Blavatnik Institute and professor of neurology at Boston Children’s Hospital. Lee is co-senior author on the paper with Christopher Harvey, professor of neurobiology at HMS, and Stefano Panzeri, professor at the University Medical Center Hamburg-Eppendorf.

In the study, rats were tasked with navigating a maze to find a reward. The researchers found that the mouse’s decision to go left or right activated sequential groups of neurons, resulting in the suppression of neurons associated with the opposite choice.

These specific connections between groups of neurons can help embody decisions by closing neural pathways to alternative options, Lee said.

A productive collaboration ensues.

It was a chance meeting on a bench outside their building during a fire drill that made Harvey and Lee realize the complementary nature of their work. That day, they formed a collaboration that led to new work.

The Harvey lab uses mice to study the behavioral and functional aspects of decision making. Common experiments involve placing a mouse in a virtual reality maze and recording neural activity as it makes decisions. Such experiments have shown that separate, but intermingled, sets of neurons fire when an animal chooses left versus right.

Lee works in a new field of neuroscience called connectomics, which aims to comprehensively map the connections between neurons in the brain. The goal, he said, is to figure out “which neurons are talking to each other, and how neurons are organized into networks.”

By combining their expertise, Harvey and Lee were able to delve deeper into the different types of neurons involved in decision-making and how these neurons are connected.

Choice of direction

The new research focused on an area of ​​the brain called the posterior parietal cortex — which Lee describes as an “integrative hub” that brings together multiple senses to help animals make decisions. Receives and processes information.

“We were interested in understanding how neural dynamics are generated in a region of the brain that is important for navigational decision-making,” Lee said. “We’re looking for principles of connectivity — simple principles that underlie the brain’s computations when making decisions.”

The Harvey lab recorded neural activity as mice ran a T-shaped maze in virtual reality. A cue, which occurred several seconds earlier, indicated to the rats whether the reward would be in T’s left or right arm.

By combining the methods, the researchers distinguished excitatory neurons — those that stimulate other cells — from inhibitory neurons, which suppress other cells. They found that a specific set of excitatory neurons fired when a mouse decided to turn right, and that these “right-turn” neurons activated a set of inhibitory neurons that “left-turn” neurons. “Inhibited activity in neurons. The opposite was true when a rat decided to turn left.

“As the animal is expressing one choice, the wiring of the neuronal circuit can help stabilize that choice by suppressing the other choice,” Lee said. “This may be a mechanism that helps the animal maintain judgment and prevents ‘mental changes’.”

These findings need to be confirmed in humans, though Lee expects some conservation across species.

The researchers see several directions for future research. One is exploring connections between neurons involved in decision-making in other regions of the brain.

We used these combined experimental techniques to find one principle of connectivity, and now we want to find others,” Li said.

Harvard University filed a patent application for GridTape (WO2017184621A1) with Lee, Hildebrand, and Graham as inventors and negotiated licensing agreements with interested partners.