Prefrontal chandelier cells encode stimulus salience to influence learning in male mice

Detecting and utilizing salience information are essential for organisms to prioritize behaviorally relevant stimuli. While the prefrontal cortex is critical for cognition and learning, how it leverages salience information remains unclear. We report that chandelier cells (ChCs) in the medial prefrontal cortex (mPFC), a unique GABAergic interneuron, encode salience information and influence learning. Using cell-type-specific calcium signal recording in male mice, we demonstrate that ChCs respond robustly to stimuli across modalities, with responses dependent on stimulus salience, as determined by novelty and intensity. Circuit-specific manipulations reveal that ChC salience coding is attributable to synaptic inputs from the anterior insular cortex and paraventricular thalamus. Furthermore, ChCs acquire salience-coding property for behaviorally relevant stimuli through associative learning. Notably, bidirectional manipulations of ChC-mediated salience detection correspondingly led to improved or impaired associative learning. Together, these findings establish mPFC ChCs as a key circuit element for processing salience information to shape learning and behavior.