# The medial prefrontal cortex encodes procedural rules as sequential neuronal activity dynamics

## TL;DR

This study shows that the medial prefrontal cortex uses sequential neuron activity to encode procedural rules, updating these sequences as learning progresses.

## Contribution

The study introduces a novel method, iSeq, to detect temporal neuronal sequences and reveals how rule learning dynamically reorganizes neuronal activity.

## Key findings

- Neuronal sequences in the medial prefrontal cortex encode procedural rules during learning.
- The composition of neuronal sequences changes as mice master a rule, predicting reward acquisition success or failure.
- Learning procedural rules involves continuous updating of neuronal activity dynamics in the medial prefrontal cortex.

## Abstract

The prefrontal cortex plays a crucial role in procedural rule learning; however, the specific neuronal mechanism through which it represents rules is unknown. We hypothesized that sequential neuronal activities in the prefrontal cortex encode these rules. To investigate this, we recorded neuronal activities in the medial prefrontal cortex of mice during rule learning using Ca2+ imaging. We utilized a method based on convolutional negative matrix factorization, iSeq, to automatically detect temporal neuronal sequences in the recorded data. As rule learning advanced, these neuronal sequences began to encode critical information for rule execution. In mice that had mastered the rule, the dynamics of neuronal sequences could predict success and failure of reward acquisition. Furthermore, the composition of cell populations within the neuronal sequences was rearranged throughout the learning process. These findings suggest that as animals learn a rule, the medial prefrontal cortex continually updates its neuronal sequences to assign significance to behavioural actions crucial for reward acquisition.

The online version contains supplementary material available at 10.1186/s13041-025-01230-w.