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5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze

The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter be...

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Autores principales: Karabeg, Margherita M., Grauthoff, Sandra, Kollert, Sina Y., Weidner, Magdalena, Heiming, Rebecca S., Jansen, Friederike, Popp, Sandy, Kaiser, Sylvia, Lesch, Klaus-Peter, Sachser, Norbert, Schmitt, Angelika G., Lewejohann, Lars
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805519/
https://www.ncbi.nlm.nih.gov/pubmed/24167611
http://dx.doi.org/10.1371/journal.pone.0078238
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author Karabeg, Margherita M.
Grauthoff, Sandra
Kollert, Sina Y.
Weidner, Magdalena
Heiming, Rebecca S.
Jansen, Friederike
Popp, Sandy
Kaiser, Sylvia
Lesch, Klaus-Peter
Sachser, Norbert
Schmitt, Angelika G.
Lewejohann, Lars
author_facet Karabeg, Margherita M.
Grauthoff, Sandra
Kollert, Sina Y.
Weidner, Magdalena
Heiming, Rebecca S.
Jansen, Friederike
Popp, Sandy
Kaiser, Sylvia
Lesch, Klaus-Peter
Sachser, Norbert
Schmitt, Angelika G.
Lewejohann, Lars
author_sort Karabeg, Margherita M.
collection PubMed
description The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised alertness, possibly impeding optimal learning performance in the more stressful WM.
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spelling pubmed-38055192013-10-28 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze Karabeg, Margherita M. Grauthoff, Sandra Kollert, Sina Y. Weidner, Magdalena Heiming, Rebecca S. Jansen, Friederike Popp, Sandy Kaiser, Sylvia Lesch, Klaus-Peter Sachser, Norbert Schmitt, Angelika G. Lewejohann, Lars PLoS One Research Article The purpose of this study was to evaluate whether spatial hippocampus-dependent learning is affected by the serotonergic system and stress. Therefore, 5-HTT knockout (-/-), heterozygous (+/-) and wildtype (+/+) mice were subjected to the Barnes maze (BM) and the Morris water maze (WM), the latter being discussed as more aversive. Additionally, immediate early gene (IEG) expression, hippocampal adult neurogenesis (aN), and blood plasma corticosterone were analyzed. While the performance of 5-HTT-/- mice in the BM was undistinguishable from both other genotypes, they performed worse in the WM. However, in the course of the repeated WM trials 5-HTT-/- mice advanced to wildtype level. The experience of a single trial of either the WM or the BM resulted in increased plasma corticosterone levels in all genotypes. After several trials 5-HTT-/- mice exhibited higher corticosterone concentrations compared with both other genotypes in both tests. Corticosterone levels were highest in 5-HTT-/- mice tested in the WM indicating greater aversiveness of the WM and a greater stress sensitivity of 5-HTT deficient mice. Quantitative immunohistochemistry in the hippocampus revealed increased cell counts positive for the IEG products cFos and Arc as well as for proliferation marker Ki67 and immature neuron marker NeuroD in 5-HTT-/- mice compared to 5-HTT+/+ mice, irrespective of the test. Most differences were found in the suprapyramidal blade of the dentate gyrus of the septal hippocampus. Ki67-immunohistochemistry revealed a genotype x environment interaction with 5-HTT genotype differences in naïve controls and WM experience exclusively yielding more Ki67-positive cells in 5-HTT+/+ mice. Moreover, in 5-HTT-/- mice we demonstrate that learning performance correlates with the extent of aN. Overall, higher baseline IEG expression and increased an in the hippocampus of 5-HTT-/- mice together with increased stress sensitivity may constitute the neurobiological correlate of raised alertness, possibly impeding optimal learning performance in the more stressful WM. Public Library of Science 2013-10-22 /pmc/articles/PMC3805519/ /pubmed/24167611 http://dx.doi.org/10.1371/journal.pone.0078238 Text en © 2013 Karabeg et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Karabeg, Margherita M.
Grauthoff, Sandra
Kollert, Sina Y.
Weidner, Magdalena
Heiming, Rebecca S.
Jansen, Friederike
Popp, Sandy
Kaiser, Sylvia
Lesch, Klaus-Peter
Sachser, Norbert
Schmitt, Angelika G.
Lewejohann, Lars
5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
title 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
title_full 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
title_fullStr 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
title_full_unstemmed 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
title_short 5-HTT Deficiency Affects Neuroplasticity and Increases Stress Sensitivity Resulting in Altered Spatial Learning Performance in the Morris Water Maze but Not in the Barnes Maze
title_sort 5-htt deficiency affects neuroplasticity and increases stress sensitivity resulting in altered spatial learning performance in the morris water maze but not in the barnes maze
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3805519/
https://www.ncbi.nlm.nih.gov/pubmed/24167611
http://dx.doi.org/10.1371/journal.pone.0078238
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