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Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice

Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models,...

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Autores principales: Raveau, Matthieu, Polygalov, Denis, Boehringer, Roman, Amano, Kenji, Yamakawa, Kazuhiro, McHugh, Thomas J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841929/
https://www.ncbi.nlm.nih.gov/pubmed/29485402
http://dx.doi.org/10.7554/eLife.31543
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author Raveau, Matthieu
Polygalov, Denis
Boehringer, Roman
Amano, Kenji
Yamakawa, Kazuhiro
McHugh, Thomas J
author_facet Raveau, Matthieu
Polygalov, Denis
Boehringer, Roman
Amano, Kenji
Yamakawa, Kazuhiro
McHugh, Thomas J
author_sort Raveau, Matthieu
collection PubMed
description Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes. These changes lead to poorer spatial coding during exploration and less coordinated activity during sharp-wave ripples, events involved in memory consolidation. Further, the density of CA1 inhibitory neurons expressing neuropeptide Y, a population key for the generation of pyramidal cell bursts, were significantly increased in Dp(16)1Yey mice. Our data refine the ‘over-suppression’ theory of Down syndrome pathophysiology and suggest specific neuronal subtypes involved in hippocampal dysfunction in these model mice.
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spelling pubmed-58419292018-03-09 Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice Raveau, Matthieu Polygalov, Denis Boehringer, Roman Amano, Kenji Yamakawa, Kazuhiro McHugh, Thomas J eLife Neuroscience Down syndrome, the leading genetic cause of intellectual disability, results from an extra-copy of chromosome 21. Mice engineered to model this aneuploidy exhibit Down syndrome-like memory deficits in spatial and contextual tasks. While abnormal neuronal function has been identified in these models, most studies have relied on in vitro measures. Here, using in vivo recording in the Dp(16)1Yey model, we find alterations in the organization of spiking of hippocampal CA1 pyramidal neurons, including deficits in the generation of complex spikes. These changes lead to poorer spatial coding during exploration and less coordinated activity during sharp-wave ripples, events involved in memory consolidation. Further, the density of CA1 inhibitory neurons expressing neuropeptide Y, a population key for the generation of pyramidal cell bursts, were significantly increased in Dp(16)1Yey mice. Our data refine the ‘over-suppression’ theory of Down syndrome pathophysiology and suggest specific neuronal subtypes involved in hippocampal dysfunction in these model mice. eLife Sciences Publications, Ltd 2018-02-27 /pmc/articles/PMC5841929/ /pubmed/29485402 http://dx.doi.org/10.7554/eLife.31543 Text en © 2018, Raveau et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Neuroscience
Raveau, Matthieu
Polygalov, Denis
Boehringer, Roman
Amano, Kenji
Yamakawa, Kazuhiro
McHugh, Thomas J
Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice
title Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice
title_full Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice
title_fullStr Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice
title_full_unstemmed Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice
title_short Alterations of in vivo CA1 network activity in Dp(16)1Yey Down syndrome model mice
title_sort alterations of in vivo ca1 network activity in dp(16)1yey down syndrome model mice
topic Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5841929/
https://www.ncbi.nlm.nih.gov/pubmed/29485402
http://dx.doi.org/10.7554/eLife.31543
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