Neural competition between prefrontal and auditory cortex constrains novel sound strategy learning.

Authors

Kai Lu, Kelvin T Wong, Chengcheng J Yang, Lin N Zhou, Yike T Shi, Maya L Costello, Robert C Liu

Published in

Science advances. Volume 12. Issue 32. Pages eaeb3005. Aug 07, 2026. Epub Aug 07, 2026.

Abstract

In nature, animals learn to replace predisposed behaviors with new strategies, yet the neural constraints on these transitions are unclear. Using an ethological search task in mice, we reveal medial prefrontal cortical (mPFC) neural correlates of a predisposed win-stay strategy that decays as animals learn to follow a more reliable auditory cue. Auditory cortex (ACx) activity predicts correct trial-by-trial sound-guided search, even on day one of training. This prognostic coding strengthens with learning and emerges from suppressed spiking, most pronounced in neurons tuned laterally to the cue's spectrum. Chemogenetic disruption reveals ACx contributions to improving performance. Unexpectedly, the global silencing of mPFC accelerates successful usage of sound-tracking, contrary to its canonical role in flexible or stimulus-dependent behavior. Instead, a decentralized multiexpert competition model best predicts behavior and causal perturbations. These findings suggest that mPFC implements a default strategy based on prior knowledge, which actively hinders the expression of more efficient strategies.

PMID:
42566525
Bibliographic data and abstract were imported from PubMed on 08 Aug 2026.

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