1. Neuroscience
Download icon

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
Research Article
  • Cited 0
  • Views 1,325
  • Annotations
Cite this article as: eLife 2021;10:e67267 doi: 10.7554/eLife.67267

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.

Metrics

  • 1,325
    Page views
  • 159
    Downloads
  • 0
    Citations

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Download citations (links to download the citations from this article in formats compatible with various reference manager tools)

Open citations (links to open the citations from this article in various online reference manager services)

Further reading

    1. Neuroscience
    Debora Fusca, Peter Kloppenburg
    Research Article

    Local interneurons (LNs) mediate complex interactions within the antennal lobe, the primary olfactory system of insects, and the functional analog of the vertebrate olfactory bulb. In the cockroach Periplaneta americana, as in other insects, several types of LNs with distinctive physiological and morphological properties can be defined. Here, we combined whole-cell patch-clamp recordings and Ca2+ imaging of individual LNs to analyze the role of spiking and nonspiking LNs in inter- and intraglomerular signaling during olfactory information processing. Spiking GABAergic LNs reacted to odorant stimulation with a uniform rise in [Ca2+]i in the ramifications of all innervated glomeruli. In contrast, in nonspiking LNs, glomerular Ca2+ signals were odorant specific and varied between glomeruli, resulting in distinct, glomerulus-specific tuning curves. The cell type-specific differences in Ca2+ dynamics support the idea that spiking LNs play a primary role in interglomerular signaling, while they assign nonspiking LNs an essential role in intraglomerular signaling.

    1. Neuroscience
    Wanhui Sheng et al.
    Research Article Updated

    Hypothalamic oxytocinergic magnocellular neurons have a fascinating ability to release peptide from both their axon terminals and from their dendrites. Existing data indicates that the relationship between somatic activity and dendritic release is not constant, but the mechanisms through which this relationship can be modulated are not completely understood. Here, we use a combination of electrical and optical recording techniques to quantify activity-induced calcium influx in proximal vs. distal dendrites of oxytocinergic magnocellular neurons located in the paraventricular nucleus of the hypothalamus (OT-MCNs). Results reveal that the dendrites of OT-MCNs are weak conductors of somatic voltage changes; however, activity-induced dendritic calcium influx can be robustly regulated by both osmosensitive and non-osmosensitive ion channels located along the dendritic membrane. Overall, this study reveals that dendritic conductivity is a dynamic and endogenously regulated feature of OT-MCNs that is likely to have substantial functional impact on central oxytocin release.