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Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury

Traumatic brain injury (TBI) increases hippocampal neurogenesis, which may contribute to cognitive recovery after injury. However, it is unknown whether TBI-induced adult-born neurons mature normally and functionally integrate into the hippocampal network. We assessed the generation, morphology, and...

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Autores principales: Villasana, Laura E., Kim, Kristine N., Westbrook, Gary L., Schnell, Eric
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Society for Neuroscience 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603252/
https://www.ncbi.nlm.nih.gov/pubmed/26478908
http://dx.doi.org/10.1523/ENEURO.0056-15.2015
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author Villasana, Laura E.
Kim, Kristine N.
Westbrook, Gary L.
Schnell, Eric
author_facet Villasana, Laura E.
Kim, Kristine N.
Westbrook, Gary L.
Schnell, Eric
author_sort Villasana, Laura E.
collection PubMed
description Traumatic brain injury (TBI) increases hippocampal neurogenesis, which may contribute to cognitive recovery after injury. However, it is unknown whether TBI-induced adult-born neurons mature normally and functionally integrate into the hippocampal network. We assessed the generation, morphology, and synaptic integration of new hippocampal neurons after a controlled cortical impact (CCI) injury model of TBI. To label TBI-induced newborn neurons, we used 2-month-old POMC-EGFP mice, which transiently and specifically express EGFP in immature hippocampal neurons, and doublecortin-CreER(T2) transgenic mice crossed with Rosa26-CAG-tdTomato reporter mice, to permanently pulse-label a cohort of adult-born hippocampal neurons. TBI increased the generation, outward migration, and dendritic complexity of neurons born during post-traumatic neurogenesis. Cells born after TBI had profound alterations in their dendritic structure, with increased dendritic branching proximal to the soma and widely splayed dendritic branches. These changes were apparent during early dendritic outgrowth and persisted as these cells matured. Whole-cell recordings from neurons generated during post-traumatic neurogenesis demonstrate that they are excitable and functionally integrate into the hippocampal circuit. However, despite their dramatic morphologic abnormalities, we found no differences in the rate of their electrophysiological maturation, or their overall degree of synaptic integration when compared to age-matched adult-born cells from sham mice. Our results suggest that cells born after TBI participate in information processing, and receive an apparently normal balance of excitatory and inhibitory inputs. However, TBI-induced changes in their anatomic localization and dendritic projection patterns could result in maladaptive network properties.
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spelling pubmed-46032522015-10-16 Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury Villasana, Laura E. Kim, Kristine N. Westbrook, Gary L. Schnell, Eric eNeuro New Research Traumatic brain injury (TBI) increases hippocampal neurogenesis, which may contribute to cognitive recovery after injury. However, it is unknown whether TBI-induced adult-born neurons mature normally and functionally integrate into the hippocampal network. We assessed the generation, morphology, and synaptic integration of new hippocampal neurons after a controlled cortical impact (CCI) injury model of TBI. To label TBI-induced newborn neurons, we used 2-month-old POMC-EGFP mice, which transiently and specifically express EGFP in immature hippocampal neurons, and doublecortin-CreER(T2) transgenic mice crossed with Rosa26-CAG-tdTomato reporter mice, to permanently pulse-label a cohort of adult-born hippocampal neurons. TBI increased the generation, outward migration, and dendritic complexity of neurons born during post-traumatic neurogenesis. Cells born after TBI had profound alterations in their dendritic structure, with increased dendritic branching proximal to the soma and widely splayed dendritic branches. These changes were apparent during early dendritic outgrowth and persisted as these cells matured. Whole-cell recordings from neurons generated during post-traumatic neurogenesis demonstrate that they are excitable and functionally integrate into the hippocampal circuit. However, despite their dramatic morphologic abnormalities, we found no differences in the rate of their electrophysiological maturation, or their overall degree of synaptic integration when compared to age-matched adult-born cells from sham mice. Our results suggest that cells born after TBI participate in information processing, and receive an apparently normal balance of excitatory and inhibitory inputs. However, TBI-induced changes in their anatomic localization and dendritic projection patterns could result in maladaptive network properties. Society for Neuroscience 2015-09-28 /pmc/articles/PMC4603252/ /pubmed/26478908 http://dx.doi.org/10.1523/ENEURO.0056-15.2015 Text en Copyright 2015 © Villasana et al. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed.
spellingShingle New Research
Villasana, Laura E.
Kim, Kristine N.
Westbrook, Gary L.
Schnell, Eric
Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury
title Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury
title_full Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury
title_fullStr Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury
title_full_unstemmed Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury
title_short Functional Integration of Adult-Born Hippocampal Neurons after Traumatic Brain Injury
title_sort functional integration of adult-born hippocampal neurons after traumatic brain injury
topic New Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603252/
https://www.ncbi.nlm.nih.gov/pubmed/26478908
http://dx.doi.org/10.1523/ENEURO.0056-15.2015
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