title: Amygdala-dependent fear memory consolidation via miR-34a and Notch signaling.
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.
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA; Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Atlanta, GA 30329, USA. Electronic address: bdias@emory.edu.
authors.forename: Brian George
authors.initials: BG
authors.lastname: Dias
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA; Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: Jared Vega
authors.initials: JV
authors.lastname: Goodman
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA; Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: Ranbir
authors.initials: R
authors.lastname: Ahluwalia
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA; Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: Audrey Elizabeth
authors.initials: AE
authors.lastname: Easton
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA; Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Atlanta, GA 30329, USA.
authors.forename: Raül
authors.initials: R
authors.lastname: Andero
authors.affiliation: Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30329, USA; Center for Behavioral Neuroscience, Yerkes National Primate Research Center, Atlanta, GA 30329, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
authors.forename: Kerry James
authors.initials: KJ
authors.lastname: Ressler
mesh_terms: D000679:Amygdala / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology*; D000818:Animals; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology*; D015536:Down-Regulation; D005239:Fear / Q000502:physiology*; D008297:Male; D008568:Memory / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D051880:Receptors, Notch / Q000378:metabolism / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: C551848:MIRN34a microRNA, mouse; D035683:MicroRNAs; D051880:Receptors, Notch