Brain cells form multiple coordinate systems to guide behavioral actions

Neuroscientists have discovered brain cells that form multiple coordinate systems to tell us ‘where we are’ in a range of behaviors. These cells can play different sequences of actions, just as a music box can be configured to play different sequences of notes. The findings help us understand the algorithms used by the brain to flexibly generate complex behaviors such as planning and reasoning, and could be useful for understanding how such processes go awry in psychiatric conditions such as schizophrenia.

The research, published today in Nature, outlines how scientists from UCL’s Sainsbury Wellcome Center and the University of Oxford studied mice that learned different behavioral sequences but with the same structure. This allowed the team to discover how mice generalize structures to new tasks, a hallmark of intelligent behavior.

Every day we solve new problems by generalizing from our knowledge. Take cooking for example. When faced with a new recipe, you can use your background knowledge of similar recipes to deduce what steps are required, even if you’ve never prepared the meal before. We wanted to understand at a detailed cellular level how the brain achieves this and from this brain activity also deduce the algorithms used to solve this problem.”

Dr. Mohamady El Gaby, first author of the study and postdoctoral neuroscientist in the Behrens lab at the Sainsbury Wellcome Center at UCL and Nuffield Department of Clinical Neurosciences, University of Oxford

The researchers gave mice a series of four target locations. Although the details of the sequences were different, the general structure was the same. Mice moved between target locations (ABC and D), which repeated in a loop.

‘After experiencing enough sequences, the mice did something remarkable: they guessed a part of the sequence they had never experienced before. When they reached D for the first time in a new location, they knew they had to head straight back to A. This action couldn’t be remembered, because it was never experienced in the first place! Instead, it is evidence that mice know the general structure of the task and can track their “position” in behavioral coordinates,” Dr. El Gaby explained.

To understand how the mice learned the overall structure of the task, the researchers used silicon probes that allowed them to record the activity of multiple individual cells in a part of the brain called the medial frontal cortex. They found that the cells jointly mapped out the animal’s ‘goal progress’. For example, one cell may fire when the animal is 70% of the way to its goal, regardless of where the goal is or how far it takes to reach it.

“We found that the cells tracked the animal’s behavioral position relative to concrete actions. If we think of the cooking analogy, the cells were concerned with progress toward subgoals such as chopping the vegetables. A subset of the cells was also aligned to map progress to the overall goal, such as preparing the meal. The ‘goal progress’ cells therefore effectively act as flexible building blocks that come together to build a behavioral coordinate system,” says Dr. El Gaby.

In fact, the team discovered that the cells form multiple coordinate systems, each telling the animal where it is in relation to a specific action. In a similar way to a music box that can be configured to play any series of notes, the brain can instead “play” behavioral actions.

The team is now trying to understand how these activity patterns are built into the brain’s connections, both when learning new behaviors and how they arise in the developing brain. Furthermore, early work from the group and their collaborators suggests that similar brain activity is present in equivalent circuits in healthy people. This has encouraged the team to work with psychiatrists to understand how these processes are affected in conditions such as schizophrenia, where the same brain circuits are known to be involved. This could help explain why people with schizophrenia overestimate their progress toward delusional goals.

This research was supported by a Wellcome Trust PhD Studentship (220047/Z/19/Z), Wellcome Principal Research Fellowship (219525/Z/19/Z), Wellcome Collaborator Award (214314/Z/18/Z), The Wellcome Center for Integrative Neuroimaging and Wellcome Center for Human Neuroimaging core funding from the Wellcome Trust (203139/Z/16/Z, 203147/Z/16/Z), the Sir Henry Wellcome Post-doctoral Fellowship (222817/Z/21/Z) , the Gatsby Charitable Foundation, the Wellcome Trust Career Development Prize (225926/Z/22/Z) and a Wellcome trust SRF (202831/Z/16/Z).