What is it about?

A new study led by researchers at the National Institutes of Health provides insight into how the brain switches between action and inhibition in response to changing situations. Using calcium imaging and innovative decoding tools in rats during reward learning, the team identified distinct patterns of activated brain cells called “ensembles” that act like QR codes: one that drives behavior (such as pressing a lever for food) behavior or suppresses the behavior when expected rewards are withheld. The researchers recorded the activity of hundreds of brain cells in individual rats across three phases: during lever pressing for food reward (Training), during learning to stop pressing when the reward was removed (Extinction), and when pressing resumed after a small, non-contingent reward was reintroduced (Reinstatement). They applied computational tools to (1) predict behavior from brain activity and (2) simulate the effects of removing specific sets of activated neurons from each rat. These analyses showed that distinct and non-overlapping ensembles were active during Training and Extinction, suggesting that the brain recruits unique neural populations for opposing learned behaviors. When the behavior returned during Reinstatement, these same ensembles were re-engaged, indicating a potential neural basis for relapse.

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Why is it important?

Learning whether to initiate an action, or not to, is essential for survival, and our brains integrate past experiences with new information to adapt to changing environments. This study provides a framework for understanding how the brain can encode opposing learned behaviors in the same brain region, using distinct groups of neurons for each. These findings help clarify how the brain supports behavioral flexibility and sheds light on processes involved in learning, extinction, and relapse. Understanding how the brain encodes multiple, sometimes conflicting, associations could inform future research on addiction, anxiety, depression, and other conditions where behavioral control is disrupted.

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This page is a summary of: Distinct prelimbic cortex ensembles encode response execution and inhibition, Proceedings of the National Academy of Sciences, September 2025, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2505378122.
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