Evidence map›Paper›PMID 24939839›Full record

ArticleLearning & memory (Cold Spring Harbor, N.Y.)2014

NMDA receptor- and ERK-dependent histone methylation changes in the lateral amygdala bidirectionally regulate fear memory formation.

Swati Gupta-Agarwal, Timothy J Jarome, Jordan Fernandez, Farah D Lubin

Open access · diamondAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Learning & memory (Cold Spring Harbor, N.Y.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing 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

32 citing papers in PubMed, 63 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Article
  5. Article
  6. Article
  7. Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Review
  15. Article
  16. Review
  17. Review
  18. Article
  19. Review
  20. Review
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

4 authors at 1 institution in 1 country.

Swati Gupta-AgarwalDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Timothy J JaromeDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Jordan FernandezDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
Farah D LubinDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
University of Alabama at Birmingham · US

Funding

Chromatin remodeling mechanisms of gene transcription in memoryR01MH097909 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LUBIN, FARAH DOMINIQUE · 2012 to 2016
$1.9M
Epigenetic Mechanisms of Gene Regulation in Long-Term Memory FormationR00MH082106 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LUBIN, FARAH DOMINIQUE · 2009 to 2011
$737k
Chromatin Remodeling Mechanism of Gene Transcription in MemoryR56MH097909 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LUBIN, FARAH DOMINIQUE · 2018 to 2018
$502k
Epigenetic Mechanisms of Gene Regulation in Long-Term Memory FormationK99MH082106 · NIMH · UNIVERSITY OF ALABAMA AT BIRMINGHAM · PI LUBIN, FARAH DOMINIQUE · 2008 to 2008
$84k
NIMH NIH HHS K99 MH082106NIMH NIH HHS MH082106NIMH NIH HHS MH097909NIMH NIH HHS R00 MH082106NIMH NIH HHS R01 MH097909NIMH NIH HHS R56 MH097909
6 · The paper itself

Abstract

It is well established that fear memory formation requires de novo gene transcription in the amygdala. We provide evidence that epigenetic mechanisms in the form of histone lysine methylation in the lateral amygdala (LA) are regulated by NMDA receptor (NMDAR) signaling and involved in gene transcription changes necessary for fear memory consolidation. Here we found increases in histone H3 lysine 9 dimethylation (H3K9me2) levels in the LA at 1 h following auditory fear conditioning, which continued to be temporally regulated up to 25 h following behavioral training. Additionally, we demonstrate that inhibiting the H3K9me2 histone lysine methyltransferase G9a (H/KMTs-G9a) in the LA impaired fear memory, while blocking the H3K9me2 histone lysine demethylase LSD1 (H/KDM-LSD1) enhanced fear memory, suggesting that H3K9me2 in the LA can bidirectionally regulate fear memory formation. Furthermore, we show that NMDAR activity differentially regulated the recruitment of H/KMT-G9a, H/KDM-LSD1, and subsequent H3K9me2 levels at a target gene promoter. This was largely regulated by GluN2B- but not GluN2A-containing NMDARs via ERK activation. Moreover, fear memory deficits associated with NMDAR or ERK blockade were successfully rescued through pharmacologically inhibiting LSD1, suggesting that enhancements of H3K9me2 levels within the LA can rescue fear memory impairments that result from hypofunctioning NMDARs or loss of ERK signaling. Together, the present study suggests that histone lysine methylation regulation in the LA via NMDAR-ERK-dependent signaling is involved in fear memory formation.

Indexed as

AnimalsAssociation LearningBasolateral Nuclear ComplexConditioning, PsychologicalDizocilpine MaleateExcitatory Amino Acid AntagonistsFearHistone-Lysine N-MethyltransferaseHistonesMaleMAP Kinase Signaling SystemMemory DisordersMemory, Long-TermMethylationRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateDizocilpine MaleateEhmt2 protein, ratExcitatory Amino Acid AntagonistsHistone-Lysine N-MethyltransferaseHistonesReceptors, N-Methyl-D-Aspartate

Identifiers

PMID24939839
PMCPMC4061426
OpenAlexW2321180569

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
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.