Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner

Post-traumatic stress disorder (PTSD) is a debilitating and chronic fear-based disorder. Pavlovian fear conditioning protocols have long been utilised to manipulate and study these fear-based disorders. Contextual fear conditioning (CFC) is a particular Pavlovian conditioning procedure that pairs fe...

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Main Authors: Nicholas Chaaya, Joshua Wang, Angela Jacques, Kate Beecher, Michael Chaaya, Andrew Raymond Battle, Luke R. Johnson, Fatemeh Chehrehasa, Arnauld Belmer, Selena E. Bartlett
Format: Article
Language:English
Published: Frontiers Media S.A. 2021-07-01
Series:Frontiers in Neural Circuits
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fncir.2021.660199/full
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author Nicholas Chaaya
Nicholas Chaaya
Joshua Wang
Joshua Wang
Angela Jacques
Angela Jacques
Kate Beecher
Kate Beecher
Michael Chaaya
Michael Chaaya
Andrew Raymond Battle
Andrew Raymond Battle
Andrew Raymond Battle
Luke R. Johnson
Luke R. Johnson
Luke R. Johnson
Fatemeh Chehrehasa
Fatemeh Chehrehasa
Arnauld Belmer
Arnauld Belmer
Selena E. Bartlett
Selena E. Bartlett
author_facet Nicholas Chaaya
Nicholas Chaaya
Joshua Wang
Joshua Wang
Angela Jacques
Angela Jacques
Kate Beecher
Kate Beecher
Michael Chaaya
Michael Chaaya
Andrew Raymond Battle
Andrew Raymond Battle
Andrew Raymond Battle
Luke R. Johnson
Luke R. Johnson
Luke R. Johnson
Fatemeh Chehrehasa
Fatemeh Chehrehasa
Arnauld Belmer
Arnauld Belmer
Selena E. Bartlett
Selena E. Bartlett
author_sort Nicholas Chaaya
collection DOAJ
description Post-traumatic stress disorder (PTSD) is a debilitating and chronic fear-based disorder. Pavlovian fear conditioning protocols have long been utilised to manipulate and study these fear-based disorders. Contextual fear conditioning (CFC) is a particular Pavlovian conditioning procedure that pairs fear with a particular context. Studies on the neural mechanisms underlying the development of contextual fear memories have identified the medial prefrontal cortex (mPFC), or more specifically, the pre-limbic cortex (PL) of the mPFC as essential for the expression of contextual fear. Despite this, little research has explored the role of the PL in contextual fear memory maintenance or examined the role of neuronal mitogen-activated protein kinase (pMAPK; ERK 1/2), brain-derived neurotrophic factor (BDNF), and IBA-1 in microglia in the PL as a function of Pavlovian fear conditioning. The current study was designed to evaluate how the maintenance of two different long-term contextual fear memories leads to changes in the number of immune-positive cells for two well-known markers of neural activity (phosphorylation of MAPK and BDNF) and microglia (IBA-1). Therefore, the current experiment is designed to assess the number of immune-positive pMAPK and BDNF cells, microglial number, and morphology in the PL following CFC. Specifically, 2 weeks following conditioning, pMAPK, BDNF, and microglia number and morphology were evaluated using well-validated antibodies and immunohistochemistry (n = 12 rats per group). A standard CFC protocol applied to rats led to increases in pMAPK, BDNF expression and microglia number as compared to control conditions. Rats in the unpaired fear conditioning (UFC) procedure, despite having equivalent levels of fear to context, did not have any change in pMAPK, BDNF expression and microglia number in the PL compared to the control conditions. These data suggest that alterations in the expression of pMAPK, BDNF, and microglia in the PL can occur for up to 2 weeks following CFC. Together the data suggest that MAPK, BDNF, and microglia within the PL of the mPFC may play a role in contextual fear memory maintenance.
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spelling doaj.art-19db266e07fb4e64bc35e7bf0fde657d2022-12-21T22:42:04ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102021-07-011510.3389/fncir.2021.660199660199Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific MannerNicholas Chaaya0Nicholas Chaaya1Joshua Wang2Joshua Wang3Angela Jacques4Angela Jacques5 Kate Beecher6 Kate Beecher7Michael Chaaya8Michael Chaaya9Andrew Raymond Battle10Andrew Raymond Battle11Andrew Raymond Battle12Luke R. Johnson13Luke R. Johnson14Luke R. Johnson15Fatemeh Chehrehasa16Fatemeh Chehrehasa17Arnauld Belmer18Arnauld Belmer19Selena E. Bartlett20Selena E. Bartlett21School of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaUniversity of Queensland Diamantina Institute, Translational Research Institute, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Psychology and Counselling, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaCenter for the Study of Traumatic Stress, Department of Psychiatry, USU School of Medicine, Bethesda, MD, United StatesTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Biomedical Science, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaSchool of Clinical Sciences, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaTranslational Research Institute, Faculty of Health, Queensland University of Technology, Brisbane, QLD, AustraliaPost-traumatic stress disorder (PTSD) is a debilitating and chronic fear-based disorder. Pavlovian fear conditioning protocols have long been utilised to manipulate and study these fear-based disorders. Contextual fear conditioning (CFC) is a particular Pavlovian conditioning procedure that pairs fear with a particular context. Studies on the neural mechanisms underlying the development of contextual fear memories have identified the medial prefrontal cortex (mPFC), or more specifically, the pre-limbic cortex (PL) of the mPFC as essential for the expression of contextual fear. Despite this, little research has explored the role of the PL in contextual fear memory maintenance or examined the role of neuronal mitogen-activated protein kinase (pMAPK; ERK 1/2), brain-derived neurotrophic factor (BDNF), and IBA-1 in microglia in the PL as a function of Pavlovian fear conditioning. The current study was designed to evaluate how the maintenance of two different long-term contextual fear memories leads to changes in the number of immune-positive cells for two well-known markers of neural activity (phosphorylation of MAPK and BDNF) and microglia (IBA-1). Therefore, the current experiment is designed to assess the number of immune-positive pMAPK and BDNF cells, microglial number, and morphology in the PL following CFC. Specifically, 2 weeks following conditioning, pMAPK, BDNF, and microglia number and morphology were evaluated using well-validated antibodies and immunohistochemistry (n = 12 rats per group). A standard CFC protocol applied to rats led to increases in pMAPK, BDNF expression and microglia number as compared to control conditions. Rats in the unpaired fear conditioning (UFC) procedure, despite having equivalent levels of fear to context, did not have any change in pMAPK, BDNF expression and microglia number in the PL compared to the control conditions. These data suggest that alterations in the expression of pMAPK, BDNF, and microglia in the PL can occur for up to 2 weeks following CFC. Together the data suggest that MAPK, BDNF, and microglia within the PL of the mPFC may play a role in contextual fear memory maintenance.https://www.frontiersin.org/articles/10.3389/fncir.2021.660199/fullfearlearning and memoryplasticityprelimbic cortexbrain derived neurotrophic factor (BDNF)
spellingShingle Nicholas Chaaya
Nicholas Chaaya
Joshua Wang
Joshua Wang
Angela Jacques
Angela Jacques
Kate Beecher
Kate Beecher
Michael Chaaya
Michael Chaaya
Andrew Raymond Battle
Andrew Raymond Battle
Andrew Raymond Battle
Luke R. Johnson
Luke R. Johnson
Luke R. Johnson
Fatemeh Chehrehasa
Fatemeh Chehrehasa
Arnauld Belmer
Arnauld Belmer
Selena E. Bartlett
Selena E. Bartlett
Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner
Frontiers in Neural Circuits
fear
learning and memory
plasticity
prelimbic cortex
brain derived neurotrophic factor (BDNF)
title Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner
title_full Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner
title_fullStr Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner
title_full_unstemmed Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner
title_short Contextual Fear Memory Maintenance Changes Expression of pMAPK, BDNF and IBA-1 in the Pre-limbic Cortex in a Layer-Specific Manner
title_sort contextual fear memory maintenance changes expression of pmapk bdnf and iba 1 in the pre limbic cortex in a layer specific manner
topic fear
learning and memory
plasticity
prelimbic cortex
brain derived neurotrophic factor (BDNF)
url https://www.frontiersin.org/articles/10.3389/fncir.2021.660199/full
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