Medial prefrontal cortex encodes but is not required to generate goal-directed actions under threat.

Overview

1. Department of Neuroscience University of Connecticut School of Medicine, Farmington, United States

Abstract

Adaptive behavior under threat requires deciding when to act and when to withhold action to avoid harm, often under conditions where movement, arousal, and task demand covary. Medial prefrontal cortex (mPFC) activity is widely associated with such control, yet it remains unclear whether this activity reflects causal action generation or broader evaluative processes shaped by behavioral state. Here, we combined fiber photometry, single-cell calcium imaging, mixed-effects modeling, and optogenetic inhibition to examine how GABAergic neurons in mouse mPFC represent cues, actions, and outcomes during a series of learned avoidance tasks of increasing complexity that promote cautious responding. By explicitly controlling for baseline activity and movement, we show that much apparent task-related activity in mPFC reflects movement and cue-evoked signals that are also present in a control cortical region, the visual cortex. mPFC GABAergic neurons showed little encoding of simple avoidance contingencies but broadly encoded punished outcomes. A small subset of neurons with strong movement sensitivity encoded more demanding avoidance contingencies requiring selection between action generation and deferment. For equivalent avoidance actions, distinct neuronal populations preferentially encoded either cue onset or the action. Despite this encoding, optogenetic inhibition of mPFC had minimal effects on the learning or performance of the different contingencies. These findings reveal a dissociation between neural encoding and causal necessity, indicating that mPFC GABAergic activity primarily reflects evaluative and contextual aspects of cautious avoidance behavior rather than direct control of action execution.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Data

Datasets cited

• doi:10.5061/dryad.n2z34tnd0 — at Dryad; found in “Data availability”

Data availability

Data has been made availble on Dryad (https://doi.org/10.5061/dryad.n2z34tnd0).

The following dataset was generated:

Castro-Alamancos MA, Sajid M, Zhou J. 2026. Medial prefrontal cortex encodes but is not required to generate goal-directed actions under threat. Dryad Digital Repository.

Reproduced under the paper's license (CC BY), from the paper cited above.

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Version 1, 27 September 2026: the first record

Recorded: type, language, journal, volume, pages, dates, 3 authors, 1 keyword, 10 MeSH terms, 1 funder, 65 references.

Cite

This paper

Sajid, M. S., Zhou, J., & Castro-Alamancos, M. A. (2026). Medial prefrontal cortex encodes but is not required to generate goal-directed actions under threat. eLife, 15, RP110964. https://doi.org/10.7554/elife.110964

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