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Author Notes:

Correspondence should be addressed to BGD: bdias@emory.edu

The authors thank Dr. Dieter Edbauer for generously providing us with cloning constructs, Xinping Huang for help with lentivirus production (Viral Vector Core, Emory University), Oskar Laur for help with cloning the miR-34a sponge and scrambled control (Custom Cloning Core Facility, Emory University), Dr. Andrew Miller and members of his laboratory for use of their luminometer for the luciferase assays, Dr. Shannon Gourley and members of her laboratory for use of the BioRad Imager for Western Blot visualization, and 3 anonymous reviewers for their constructive suggestions that have strengthened this version of the manuscript.

Subject:

Research Funding:

This work was supported by funding to KJR by HHMI and Burroughs Wellcome Fund.

The Viral Vector Core of the Emory Neuroscience NINDS Core Facilities is supported by grant P30NS055077.

This project was partially funded by the National Center for Research Resources P51RR000165 and is currently supported by the Office of Research Infrastructure Programs/OD P51OD011132 to the Yerkes National Primate Research Center.

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • LONG-TERM-MEMORY
  • MECHANISMS
  • MICRORNAS
  • EXTINCTION
  • EXPRESSION
  • PLASTICITY
  • ANXIETY
  • STRESS
  • TARGET

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

Tools:

Journal Title:

Neuron

Volume:

Volume 83, Number 4

Publisher:

, Pages 906-918

Type of Work:

Article | Post-print: After Peer Review

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.

Copyright information:

© 2014 Elsevier Inc.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (http://creativecommons.org/licenses/by-nc-nd/4.0/).

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