Evidence map›Paper›PMID 42642653›Full record

ArticleNature neuroscience2026

Social isolation recruits amygdala-medial prefrontal cortex projections to escalate alcohol drinking in male mice.

Reesha R Patel, Kelly N Kim, Makenzie Patarino, Rachelle Pamintuan, Felix H Taschbach, Hao Li, Bitna Joo, Anna Pallé, Xianru Yu, Christopher R Lee and 14 more

Abstract read
In one paragraph

Article in Nature neuroscience, 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

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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

24 authors.

Reesha R Patel *Salk Institute for Biological Studies, La Jolla, CA, USA. reesha.patel@northwestern.edu.ORCID http://orcid.org/0000-0003-3913-6311
Kelly N Kim *Salk Institute for Biological Studies, La Jolla, CA, USA.
Makenzie PatarinoSalk Institute for Biological Studies, La Jolla, CA, USA.
Rachelle PamintuanSalk Institute for Biological Studies, La Jolla, CA, USA.
Felix H TaschbachSalk Institute for Biological Studies, La Jolla, CA, USA.
Hao LiSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-8710-1290
Bitna JooSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-7063-8999
Anna PalléSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0003-0389-1366
Xianru YuStephen M. Stahl Center for Psychiatric Neuroscience, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Christopher R LeeSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-5952-9924
Aniek van HoekSalk Institute for Biological Studies, La Jolla, CA, USA.
Jesse WhiteSalk Institute for Biological Studies, La Jolla, CA, USA.
Rogelio CastroSalk Institute for Biological Studies, La Jolla, CA, USA.
Christian CazaresSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-8899-2109
Raymundo L MirandaSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0009-0009-9694-1545
Caroline JiaSalk Institute for Biological Studies, La Jolla, CA, USA.
Jeremy DelahantySalk Institute for Biological Studies, La Jolla, CA, USA.
Kanha BatraSalk Institute for Biological Studies, La Jolla, CA, USA.
Laurel R KeyesSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-5433-9948
Avraham LibsterSalk Institute for Biological Studies, La Jolla, CA, USA.
Romy WichmannSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0002-4506-8813
Talmo D PereiraSalk Institute for Biological Studies, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-9075-8365
Marcus K BennaUniversity of California San Diego, La Jolla, CA, USA.ORCID http://orcid.org/0000-0001-8100-2857
Kay M TyeSalk Institute for Biological Studies, La Jolla, CA, USA. tye@salk.edu.ORCID http://orcid.org/0000-0002-2435-0182

Funding

Neural Circuit Mechanisms of Social Homeostasis in Individuals and Supraorganismal Social GroupsDP1AT009925 · NCCIH · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI TYE, KAY MAXINE · 2017 to 2021
$6.4M
Corticolimbic Neuroimmune Determinants of Social Stress-Associated Alcohol DrinkingR00AA029180 · NIAAA · NORTHWESTERN UNIVERSITY AT CHICAGO · PI PATEL, REESHA · 2023 to 2025
$793k
Cytokine-mediated tuning of neural circuits underlying avoidance behaviorR01MH139476 · NIMH · NORTHWESTERN UNIVERSITY · PI Reesha Patel · 2026 to 2026
$708k
Corticolimbic Neuroimmune Determinants of Social Stress-Associated Alcohol DrinkingK99AA029180 · NIAAA · SALK INSTITUTE FOR BIOLOGICAL STUDIES · PI PATEL, REESHA · 2022 to 2023
$345k
NCCIH NIH HHS DP1 AT009925NIAAA NIH HHS K99 AA029180NIAAA NIH HHS R00 AA029180NIMH NIH HHS R01 MH139476
6 · The paper itself

Abstract

Social isolation profoundly alters motivation and increases vulnerability to alcohol misuse in humans, yet the underlying neural mechanisms remain unclear. Here we show that isolation escalates alcohol drinking in male mice but suppresses it in females. Whole-cell recordings revealed that neurons in the basolateral amygdala projecting to the medial prefrontal cortex (BLA-mPFC) track alcohol intake in both sexes. Isolation increased BLA-mPFC excitability in males but decreased it in females, mirroring their opposite behavioral adaptations. Given this divergence, we focused subsequent mechanistic studies on males to isolate neural pathway-level drivers of escalated alcohol intake. Cellular-resolution calcium imaging showed that activity in BLA-mPFC neurons encodes and predicts alcohol drinking, and optogenetic activation of this pathway increased alcohol intake. Simultaneous optogenetics and calcium imaging revealed that BLA-mPFC stimulation enhanced mPFC neuronal responses to alcohol, mimicking isolation-induced activity patterns, while photoinhibition reduced drinking in isolated mice. Together, these findings identify a BLA-mPFC pathway mechanism through which social isolation reconfigures prefrontal processing to promote alcohol intake.

Indexed as

Alcohol DrinkingAmygdalaPrefrontal CortexSocial IsolationAnimalsFemaleMaleMiceMice, Inbred C57BLNeural PathwaysNeuronsOptogenetics

Identifiers

PMID42642653
PMCPMC13633117

What OpenQuestion holds

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Registered trials

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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.