A genetic link between discriminative fear coding by the lateral amygdala, dopamine, and fear generalization

Abstract

The lateral amygdala (LA) acquires differential coding of predictive and non-predictive fear stimuli that is critical for proper fear memory assignment. The neurotransmitter dopamine is an important modulator of LA activity and facilitates fear memory formation, but whether dopamine neurons aid in the establishment of discriminative fear coding by the LA is unknown. NMDA-type glutamate receptors in dopamine neurons are critical for the prevention of generalized fear following an aversive experience, suggesting a potential link between a cell autonomous function of NMDAR in dopamine neurons and fear coding by the LA. Here, we utilized mice with a selective genetic inactivation functional NMDARs in dopamine neurons (DAT-NR1 KO mice) combined with behavior, in vivo electrophysiology, and ex vivo electrophysiology in LA neurons to demonstrate that plasticity underlying differential fear coding in the LA is regulated by NMDAR signaling in dopamine neurons and alterations in this plasticity is associated non-discriminative cued-fear responses.

Article and author information

Author details

  1. Graham L Jones

    Department of Psychiatry and Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Marta E Soden

    Department of Psychiatry and Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Cerise R Knakal

    Department of Psychiatry and Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Heather Lee

    Department of Psychiatry and Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Amanda S Zila

    Department of Psychiatry and Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Elliott B Merriam

    Department of Psychiatry and Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Larry S Zweifel

    Department of Psychiatry and Behavioral Sciences and the Department of Pharmacology, University of Washington, Seattle, United States
    For correspondence
    larryz@uw.edu
    Competing interests
    The authors declare that no competing interests exist.

Ethics

Animal experimentation: All experimental procedures were performed in accordance with the recommendations in the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and approved by the University of Washington Institutional Animal Care and Use Committee protocol (#4249-01). All surgical procedures were performed under isolflurane anesthesia with analagesic pretreatment.All efforts were made to minimize suffering.

Reviewing Editor

  1. Eunjoon Kim, Korea Advanced Institute of Science and Technology, Republic of Korea

Publication history

  1. Received: May 24, 2015
  2. Accepted: September 23, 2015
  3. Accepted Manuscript published: September 24, 2015 (version 1)
  4. Version of Record published: October 27, 2015 (version 2)

Copyright

© 2015, Jones et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Graham L Jones
  2. Marta E Soden
  3. Cerise R Knakal
  4. Heather Lee
  5. Amanda S Zila
  6. Elliott B Merriam
  7. Larry S Zweifel
(2015)
A genetic link between discriminative fear coding by the lateral amygdala, dopamine, and fear generalization
eLife 4:e08969.
https://doi.org/10.7554/eLife.08969

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