IGF-1 facilitates extinction of conditioned fear
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
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.
Reviewing Editor
- Inna Slutsky, Tel Aviv University, Israel
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.
Version history
- Received: February 5, 2021
- Accepted: March 31, 2021
- Accepted Manuscript published: April 1, 2021 (version 1)
- 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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