Evidence map›Paper›PMID 37491314›Full record

ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2023

Brain-Wide Projections and Differential Encoding of Prefrontal Neuronal Classes Underlying Learned and Innate Threat Avoidance.

Michael W Gongwer, Cassandra B Klune, João Couto, Benita Jin, Alexander S Enos, Rita Chen, Drew Friedmann, Laura A DeNardo

Open access · greenAbstract read
In one paragraph

Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.

0numbers the graph read from it
0cells of the map it votes in
38citing papers in PubMed
6.2field-weighted citation impact, top 3% of its field
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

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

38 citing papers in PubMed, 35 citations in OpenAlex.

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  9. Maternal experience alters brain-wide representation of infant cries.bioRxiv : the preprint server for biology · 2026
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  17. Prefrontal cortex development and its implications in mental illness.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026
    Review
  18. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 5 institutions in 3 countries.

Michael W GongwerDepartment of Physiology.
Cassandra B KluneDepartment of Physiology.
João CoutoDeparatment of Neurobiology.
Benita JinDepartment of Physiology.
Alexander S EnosDepartment of Physiology.
Rita ChenDepartment of Physiology.
Drew FriedmannCajal Neuroscience, Seattle, Washington 98102.
Laura A DeNardoDepartment of Physiology ldenardo@ucla.edu.
Czech Academy of Sciences, Institute of Physiology · CZInterScience (United States) · USCajal Neuroscience (United States) · USInstitute of Neurobiology · BGUniversity of California, Los Angeles · US

Funding

Training Grant in Neurobehavioral GeneticsT32NS048004 · NINDS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, OPHOFF, ROEL A · 2004 to 2025
$5.8M
Training Grant in Neurobehavioral GeneticsT32MH073526 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI BEARDEN, CARRIE E, GESCHWIND, DANIEL H · 2006 to 2020
$2.4M
Prefrontal circuits underlying the maturation of learned avoidanceR01MH127214 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Laura Anne DeNardo · 2022 to 2026
$2.3M
Circuit mechanisms for prefrontal control of remote memory retrievalK01MH116264 · NIMH · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DENARDO, LAURA ANNE · 2018 to 2021
$681k
NIMH NIH HHS K01 MH116264NIMH NIH HHS R01 MH127214NIMH NIH HHS T32 MH073526NINDS NIH HHS T32 NS048004
6 · The paper itself

Abstract

To understand how the brain produces behavior, we must elucidate the relationships between neuronal connectivity and function. The medial prefrontal cortex (mPFC) is critical for complex functions including decision-making and mood. mPFC projection neurons collateralize extensively, but the relationships between mPFC neuronal activity and brain-wide connectivity are poorly understood. We performed whole-brain connectivity mapping and fiber photometry to better understand the mPFC circuits that control threat avoidance in male and female mice. Using tissue clearing and light sheet fluorescence microscopy (LSFM), we mapped the brain-wide axon collaterals of populations of mPFC neurons that project to nucleus accumbens (NAc), ventral tegmental area (VTA), or contralateral mPFC (cmPFC). We present DeepTraCE (deep learning-based tracing with combined enhancement), for quantifying bulk-labeled axonal projections in images of cleared tissue, and DeepCOUNT (deep-learning based counting of objects via 3D U-net pixel tagging), for quantifying cell bodies. Anatomical maps produced with DeepTraCE aligned with known axonal projection patterns and revealed class-specific topographic projections within regions. Using TRAP2 mice and DeepCOUNT, we analyzed whole-brain functional connectivity underlying threat avoidance. PL was the most highly connected node with functional connections to subsets of PL-cPL, PL-NAc, and PL-VTA target sites. Using fiber photometry, we found that during threat avoidance, cmPFC and NAc-projectors encoded conditioned stimuli, but only when action was required to avoid threats. mPFC-VTA neurons encoded learned but not innate avoidance behaviors. Together our results present new and optimized approaches for quantitative whole-brain analysis and indicate that anatomically defined classes of mPFC neurons have specialized roles in threat avoidance.

Indexed as

BrainNeuronsAnimalsFemaleMaleMiceNeural PathwaysNucleus AccumbensPrefrontal Cortexaxondeep learninglight sheet microscopyprefrontal cortexthreat avoidancetissue clearing

Identifiers

PMID37491314
PMCPMC10423051
OpenAlexW4385252045

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.