Amygdala-Dependent Fear Memory Consolidation via miR-34a and Notch Signaling

Brian George Dias*, Jared Vega Goodman, Ranbir Ahluwalia, Audrey Elizabeth Easton, Raül Andero, Kerry James Ressler

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

77 Citations (Scopus)

Abstract

Using an array-based approach after auditory fear conditioning and microRNA (miRNA) sponge-mediated inhibition, we identified a role for miR-34a within the basolateral amygdala (BLA) in fear memory consolidation. Luciferase assays and bioinformatics suggested the Notch pathway as a target of miR-34a. mRNA and protein levels of Notch receptors and ligands are downregulated in a time- and learning-specific manner after fear conditioning in the amygdala. Systemic and stereotaxic manipulations of the Notch pathway indicated that Notch signaling in the BLA suppresses fear memory consolidation. Impairment of fear memory consolidation after inhibition of miR-34a within the BLA is rescued by inhibiting Notch signaling. Together, these data suggest that within the BLA, a transient decrease in Notch signaling, via miR-34a regulation, is important for the consolidation of fear memory. This work expands the idea that developmental molecules have roles in adult behavior and that existing interventions targeting them hold promise for treating neuropsychiatric disorders.

Original languageEnglish
Pages (from-to)906-918
Number of pages13
JournalNeuron
Volume83
Issue number4
DOIs
Publication statusPublished - 20 Aug 2014

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