Learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression

Abstract Psychological distress, including anxiety or mood disorders, emanates from the onset of chronic/unpredictable stressful events. Symptoms in the form of maladaptive behaviors are learned and difficult to treat. While the origin of stress-induced disorders seems to be where learning and stres...

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Main Authors: Jazmine D. W. Yaeger, Justin K. Achua, Clarissa D. Booth, Delan Khalid, Megan M. John, Leighton J. Ledesma, Trent L. Greschke, Ashley M. Potter, Chase B. Howe, Kevin T. Krupp, Justin P. Smith, Patrick J. Ronan, Cliff H. Summers
Format: Article
Language:English
Published: Nature Portfolio 2024-12-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-024-81590-w
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author Jazmine D. W. Yaeger
Justin K. Achua
Clarissa D. Booth
Delan Khalid
Megan M. John
Leighton J. Ledesma
Trent L. Greschke
Ashley M. Potter
Chase B. Howe
Kevin T. Krupp
Justin P. Smith
Patrick J. Ronan
Cliff H. Summers
author_facet Jazmine D. W. Yaeger
Justin K. Achua
Clarissa D. Booth
Delan Khalid
Megan M. John
Leighton J. Ledesma
Trent L. Greschke
Ashley M. Potter
Chase B. Howe
Kevin T. Krupp
Justin P. Smith
Patrick J. Ronan
Cliff H. Summers
author_sort Jazmine D. W. Yaeger
collection DOAJ
description Abstract Psychological distress, including anxiety or mood disorders, emanates from the onset of chronic/unpredictable stressful events. Symptoms in the form of maladaptive behaviors are learned and difficult to treat. While the origin of stress-induced disorders seems to be where learning and stress intersect, this relationship and molecular pathways involved remain largely unresolved. The hippocampus, studied for its role in learning, is divided into regions that designate the passage of neuronal signaling during memory formation, including dentate gyrus (DG), CA3, CA2, and CA1. Inputs into these hippocampal subregions, like those from hypothalamic orexinergic neurons, may modify learning outcomes. We have previously shown the orexin system to balance stress states, where receptor subtypes prompt opposing actions on behavior. Here, we explore the connection between hippocampal orexin receptors and learning during stress. In a social stress/learning paradigm separating mice into stress resilient and vulnerable populations, hippocampal Orx1R and Orx2R transcription is regulated in a phenotype-dependent fashion. We further identified Orx1R as highly expressed in the hilus of DG, while Orx2R is abundant in CA2. Finally, we designed an experiment where mice were provided prior exposure to a stressful environment, which ultimately modified behavior, as well as transcription of hippocampal orexin receptors.
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spelling doaj-art-8152641d1edb4b28accce40bd91d753c2025-01-05T12:29:55ZengNature PortfolioScientific Reports2045-23222024-12-0114111710.1038/s41598-024-81590-wLearned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expressionJazmine D. W. Yaeger0Justin K. Achua1Clarissa D. Booth2Delan Khalid3Megan M. John4Leighton J. Ledesma5Trent L. Greschke6Ashley M. Potter7Chase B. Howe8Kevin T. Krupp9Justin P. Smith10Patrick J. Ronan11Cliff H. Summers12Cellular Therapies and Stem Cell Biology Group, Sanford ResearchDivision of Urology, University of Colorado School of Medicine, Anschutz Medical CampusPediatrics and Rare Diseases Group, Sanford ResearchSchool of Medicine, BMP, University of PittsburghDepartment of Biology, University of South DakotaDepartment of Biology, University of South DakotaDepartment of Biology, University of South DakotaDepartment of Clinical Sciences, Colorado State UniversityNeuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South DakotaDepartment of Biology, University of South DakotaAdvanced Analytics GroupNeuroscience Group, Division of Basic Biomedical Sciences, Sanford School of Medicine, University of South DakotaDepartment of Biology, University of South DakotaAbstract Psychological distress, including anxiety or mood disorders, emanates from the onset of chronic/unpredictable stressful events. Symptoms in the form of maladaptive behaviors are learned and difficult to treat. While the origin of stress-induced disorders seems to be where learning and stress intersect, this relationship and molecular pathways involved remain largely unresolved. The hippocampus, studied for its role in learning, is divided into regions that designate the passage of neuronal signaling during memory formation, including dentate gyrus (DG), CA3, CA2, and CA1. Inputs into these hippocampal subregions, like those from hypothalamic orexinergic neurons, may modify learning outcomes. We have previously shown the orexin system to balance stress states, where receptor subtypes prompt opposing actions on behavior. Here, we explore the connection between hippocampal orexin receptors and learning during stress. In a social stress/learning paradigm separating mice into stress resilient and vulnerable populations, hippocampal Orx1R and Orx2R transcription is regulated in a phenotype-dependent fashion. We further identified Orx1R as highly expressed in the hilus of DG, while Orx2R is abundant in CA2. Finally, we designed an experiment where mice were provided prior exposure to a stressful environment, which ultimately modified behavior, as well as transcription of hippocampal orexin receptors.https://doi.org/10.1038/s41598-024-81590-wAmygdalaFamiliarityGene expressionHippocampusOrexin receptorsSpatial learning
spellingShingle Jazmine D. W. Yaeger
Justin K. Achua
Clarissa D. Booth
Delan Khalid
Megan M. John
Leighton J. Ledesma
Trent L. Greschke
Ashley M. Potter
Chase B. Howe
Kevin T. Krupp
Justin P. Smith
Patrick J. Ronan
Cliff H. Summers
Learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression
Scientific Reports
Amygdala
Familiarity
Gene expression
Hippocampus
Orexin receptors
Spatial learning
title Learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression
title_full Learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression
title_fullStr Learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression
title_full_unstemmed Learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression
title_short Learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression
title_sort learned phenotypes emerge during social stress modifying hippocampal orexin receptor gene expression
topic Amygdala
Familiarity
Gene expression
Hippocampus
Orexin receptors
Spatial learning
url https://doi.org/10.1038/s41598-024-81590-w
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