IGF-1 facilitates extinction of conditioned fear

  1. Laura E Maglio  Is a corresponding author
  2. José A Noriega-Prieto
  3. Irene B Maroto
  4. Jesús Martin-Cortecero
  5. Antonio Muñoz-Callejas
  6. Marta Callejo-Móstoles
  7. David Fernández de Sevilla  Is a corresponding author
  1. Universidad de La Laguna, Spain
  2. University of Minnesota, United States
  3. Universidad Complutense de Madrid, Spain
  4. Heidelberg University, Germany
  5. Universidad Autonoma de Madrid, Spain

Abstract

Insulin-like growth factor-1 (IGF-1) plays a key role in synaptic plasticity, spatial learning and anxiety-like behavioral processes. While IGF-1 regulates neuronal firing and synaptic transmission in many areas of the central nervous system, its signaling and consequences on excitability, synaptic plasticity, and animal behavior dependent on the prefrontal cortex remain unexplored. Here, we show that IGF-1 induces a long-lasting depression of the medium and slow post-spike afterhyperpolarization (mAHP and sAHP), increasing the excitability of layer 5 pyramidal neurons of the rat infralimbic cortex. Besides, IGF-1 mediates a presynaptic long-term depression of both inhibitory and excitatory synaptic transmission in these neurons. The net effect of this IGF-1 mediated synaptic plasticity is a long-term potentiation of the postsynaptic potentials. Moreover, we demonstrate that IGF-1 favors the fear extinction memory. These results show novel functional consequences of IGF-1 signaling, revealing IGF-1 as a key element in the control of the fear extinction memory.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files

Article and author information

Author details

  1. Laura E Maglio

    Departamento de Ciencias Médicas Básicas (Fisiología) and Instituto de Tecnologías Biomédicas (ITB), Universidad de La Laguna, Tenerife, Spain
    For correspondence
    lamaglio@ull.edu.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4760-5624
  2. José A Noriega-Prieto

    Department of Neuroscience, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Irene B Maroto

    Departamento de Bioquímica y Biología Molecular, Universidad Complutense de Madrid, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  4. Jesús Martin-Cortecero

    Institute of Physiology and Pathophys, Heidelberg University, Heidelberg, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9350-6267
  5. Antonio Muñoz-Callejas

    Anatomia Histologia y Neurociencia, Universidad Autonoma de Madrid, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  6. Marta Callejo-Móstoles

    Anatomia Histologia y Neurociencia, Universidad Autonoma de Madrid, Madrid, Spain
    Competing interests
    The authors declare that no competing interests exist.
  7. David Fernández de Sevilla

    Anatomia Histologia y Neurociencia, Universidad Autonoma de Madrid, Madrid, Spain
    For correspondence
    david.fernandezdesevilla@uam.es
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6344-0773

Funding

Ministerio de Economía, Industria y Competitividad, Gobierno de España (BFU2013-43668-P)

  • David Fernández de Sevilla

Ministerio de Economía, Industria y Competitividad, Gobierno de España (BFU2016-0802-P AEI/FEDER,UE)

  • David Fernández de Sevilla

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Animal experimentation: All animal procedures were approved by the Universidad Autónoma of Madrid Ethical Committee on Animal Welfare and conform to Spanish and European guidelines for the protection of experimental animals (Directive 2010/63/EU). An effort was made to minimize animal suffering and number.

Reviewing Editor

  1. Inna Slutsky, Tel Aviv University, Israel

Publication history

  1. Received: February 5, 2021
  2. Accepted: March 31, 2021
  3. Accepted Manuscript published: April 1, 2021 (version 1)
  4. Version of Record published: April 13, 2021 (version 2)

Copyright

© 2021, Maglio 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. Laura E Maglio
  2. José A Noriega-Prieto
  3. Irene B Maroto
  4. Jesús Martin-Cortecero
  5. Antonio Muñoz-Callejas
  6. Marta Callejo-Móstoles
  7. David Fernández de Sevilla
(2021)
IGF-1 facilitates extinction of conditioned fear
eLife 10:e67267.
https://doi.org/10.7554/eLife.67267

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