Evidence map›Paper›PMID 26503065›Full record

ArticleAlcoholism, clinical and experimental research2015

Ethanol produces corticotropin-releasing factor receptor-dependent enhancement of spontaneous glutamatergic transmission in the mouse central amygdala.

Yuval Silberman, Tracy L Fetterly, Elias K Awad, Elana J Milano, Ted B Usdin, Danny G Winder

Abstract read
In one paragraph

Article in Alcoholism, clinical and experimental research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.8field-weighted citation impact, top 32% 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

13 citing papers in PubMed, 17 citations in OpenAlex.

  1. Article
  2. Synaptic Effects Induced by Alcohol.Current topics in behavioral neurosciences · 2025
    Review
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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

6 authors at 3 institutions in 1 country.

Yuval SilbermanDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Tracy L FetterlyDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Elias K AwadDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Elana J MilanoDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Ted B UsdinSection on Fundamental Neuroscience, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland.
Danny G WinderDepartment of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee.
Vanderbilt University · USVanderbilt Health · USNational Institute of Mental Health · US

Funding

Peptide Receptor SystemsZIAMH002685 · NIMH · NATIONAL INSTITUTE OF MENTAL HEALTH · PI USDIN, TED B · 2009 to 2016
$10.0M
Research Project: Sensory and Multisensory Contributions to AutismU54HD083211 · NICHD · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DYKENS, ELISABETH MAY · 2015 to 2019
$7.1M
Alcohol action on extended amygdala glutamate synapsesR37AA019455 · NIAAA · VANDERBILT UNIVERSITY · PI WINDER, DANNY G. · 2015 to 2024
$3.9M
Periadolescent Noradrenergic Regulation in the BNSTR01DA019112 · NIDA · VANDERBILT UNIVERSITY · PI WINDER, DANNY G. · 2004 to 2014
$3.3M
Alcohol action on extended amygdala glutamate synapsesR01AA019455 · NIAAA · VANDERBILT UNIVERSITY · PI WINDER, DANNY G. · 2010 to 2014
$1.8M
Engagement of novel noradrenergic and CRF circuit interactions by chronic alcoholR00AA022937 · NIAAA · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · PI SILBERMAN, YUVAL · 2016 to 2018
$708k
Engagement of novel noradrenergic and CRF circuit interactions by chronic alcoholK99AA022937 · NIAAA · VANDERBILT UNIVERSITY · PI SILBERMAN, YUVAL · 2014 to 2015
$278k
CRF regulation of BNST target control in alcohol withdrawalF32AA020140 · NIAAA · VANDERBILT UNIVERSITY · PI SILBERMAN, YUVAL · 2010 to 2012
$153k
Intramural NIH HHSNIAAA NIH HHS AA 19455NIAAA NIH HHS AA 20140NIAAA NIH HHS AA 22937NIAAA NIH HHS F32 AA020140NIAAA NIH HHS K99 AA022937NIAAA NIH HHS R00 AA022937NIAAA NIH HHS R01 AA019455NIAAA NIH HHS R37 AA019455NICHD NIH HHS U54 HD083211NIDA NIH HHS DA 19112NIDA NIH HHS R01 DA019112NIMH NIH HHS ZIA-MH002685
6 · The paper itself

Abstract

backgroundEthanol (EtOH) modulation of central amygdala (CeA) neurocircuitry plays a key role in the development of alcoholism via activation of the corticotropin-releasing factor (CRF) receptor (CRFR) system. Previous work has predominantly focused on EtOH × CRF interactions on the CeA GABA circuitry; however, our laboratory recently showed that CRF enhances CeA glutamatergic transmission. Therefore, this study sought to determine whether EtOH modulates CeA glutamate transmission via activation of CRF signaling.

methodsThe effects of EtOH on spontaneous excitatory postsynaptic currents (sEPSCs) and basal resting membrane potentials were examined via standard electrophysiology methods in adult male C57BL/6J mice. Local ablation of CeA CRF neurons (CRF(CeAhDTR) ) was achieved by targeting the human diphtheria toxin receptor (hDTR) to CeA CRF neurons with an adeno-associated virus. Ablation was quantified post hoc with confocal microscopy. Genetic targeting of the diphtheria toxin active subunit to CRF neurons (CRF(DTA) mice) ablated CRF neurons throughout the central nervous system, as assessed by quantitative reverse transcriptase polymerase chain reaction quantification of CRF mRNA.

resultsAcute bath application of EtOH significantly increased sEPSC frequency in a concentration-dependent manner in CeA neurons, and this effect was blocked by pretreatment of co-applied CRFR1 and CRFR2 antagonists. In experiments utilizing a CRF-tomato reporter mouse, EtOH did not significantly alter the basal membrane potential of CeA CRF neurons. The ability of EtOH to enhance CeA sEPSC frequency was not altered in CRF(CeAhDTR) mice despite a ~78% reduction in CeA CRF cell counts. The ability of EtOH to enhance CeA sEPSC frequency was also not altered in the CRF(DTA) mice despite a 3-fold reduction in CRF mRNA levels.

conclusionsThese findings demonstrate that EtOH enhances spontaneous glutamatergic transmission in the CeA via a CRFR-dependent mechanism. Surprisingly, our data suggest that this action may not require endogenous CRF.

Indexed as

AnimalsCentral Amygdaloid NucleusDose-Response Relationship, DrugEthanolExcitatory Postsynaptic PotentialsGlutamic AcidHumansMaleMiceMice, 129 StrainMice, Inbred C57BLMice, TransgenicOrgan Culture TechniquesReceptors, Corticotropin-Releasing HormoneSynaptic TransmissionEthanolGlutamic AcidReceptors, Corticotropin-Releasing HormoneCentral Nucleus of the AmygdalaCRF Reporter MiceDiphtheria ToxinSelective DeletionWhole-Cell Patch-Clamp Electrophysiology

Identifiers

PMID26503065
PMCPMC4624256
OpenAlexW1929905538

What OpenQuestion holds

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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.