microRNA mir-598-3p mediates susceptibility to stress enhancement of remote fear memory.
Journal
Learning & memory (Cold Spring Harbor, N.Y.)
ISSN: 1549-5485
Titre abrégé: Learn Mem
Pays: United States
ID NLM: 9435678
Informations de publication
Date de publication:
09 2019
09 2019
Historique:
received:
19
03
2019
accepted:
10
06
2019
entrez:
17
8
2019
pubmed:
17
8
2019
medline:
18
8
2020
Statut:
epublish
Résumé
microRNAs (miRNAs) have emerged as potent regulators of learning, recent memory, and extinction. However, our understanding of miRNAs directly involved in regulating complex psychiatric conditions perpetuated by aberrant memory, such as in posttraumatic stress disorder (PTSD), remains limited. To begin to address the role of miRNAs in persistent memories, we performed small-RNA sequencing on basolateral amygdala (BLA) tissue and identified miRNAs altered by auditory fear conditioning (FC) one month after training. mir-598-3p, a highly conserved miRNA previously unstudied in the brain, was down-regulated in the BLA. Further decreasing BLA mir-598-3p levels did not increase strength of the remote fear memory. Given that stress is a critical component in PTSD, we next assessed the impact of stress and stress-enhanced fear learning (SEFL) on mir-598-3p levels, finding the miRNA is elevated in the BLA of male, but not female, mice susceptible to the effects of stress in SEFL. Accordingly, intra-BLA inhibition of mir-598-3p interfered with expression and extinction of the remote fear memory in male, but not female, mice. This effect could not be attributed to an anxiolytic effect of miRNA inhibition. Finally, bioinformatic analysis following quantitative proteomics on BLA tissue collected 30 d post-SEFL training identified putative mir-598-3p targets and related pathways mediating the differential susceptibility, with evidence for regulation of the actin cytoskeleton, the core mediator of structural plasticity. Taken together, the results suggest BLA mir-598-3p may be recruited by stress to mediate a critical switch from a salient remote fear memory to one that is enhanced and extinction-resistant.
Identifiants
pubmed: 31416909
pii: 26/9/363
doi: 10.1101/lm.048827.118
pmc: PMC6699414
doi:
Substances chimiques
MIRN598 microRNA, mouse
0
MicroRNAs
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
363-372Subventions
Organisme : NIDA NIH HHS
ID : K99 DA041469
Pays : United States
Organisme : NIDA NIH HHS
ID : R00 DA041469
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH105400
Pays : United States
Informations de copyright
© 2019 Jones et al.; Published by Cold Spring Harbor Laboratory Press.
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