Evidence map›Paper›PMID 42417528›Full record

ArticleeLife2026

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

Muhammad S Sajid, Ji Zhou, Manuel A Castro-Alamancos

Abstract read
In one paragraph

Article in eLife, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

3 authors.

Muhammad S Sajid *Department of Neuroscience University of Connecticut School of Medicine, Farmington, United States.
Ji Zhou *Department of Neuroscience University of Connecticut School of Medicine, Farmington, United States.
Manuel A Castro-AlamancosDepartment of Neuroscience University of Connecticut School of Medicine, Farmington, United States.ORCID 0000-0002-2916-9585

Funding

Sensory pathways for stimulus detection during behaviorR35NS097272 · NINDS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI CASTRO-ALAMANCOS, MANUEL A · 2017 to 2024
$4.3M
Neural mechanisms of active avoidance behaviorR01NS104810 · NINDS · UNIVERSITY OF CONNECTICUT SCH OF MED/DNT · PI CASTRO-ALAMANCOS, MANUEL A · 2018 to 2022
$2.8M
NINDS NIH HHS R01NS104810NINDS NIH HHS R35NS097272
6 · The paper itself

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.

Indexed as

Avoidance LearningGABAergic NeuronsGoalsPrefrontal CortexAnimalsCuesMaleMiceMice, Inbred C57BLOptogeneticsaction selectionavoidanceinhibitionmouseneuroscienceprefrontal cortexthreat

Identifiers

PMID42417528
PMCPMC13345635

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.