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Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits

Recent investigations of Nogo-A, a well characterized protein inhibitor of neurite outgrowth in the brain, have revealed additional functions including a role in neuropsychiatric disorders such as schizophrenia. Here we examined Nogo-A functions in mouse CA3 hippocampal circuitry. Patch clamp record...

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Autores principales: Berry, Stewart, Weinmann, Oliver, Fritz, Ann-Kristina, Rust, Ruslan, Wolfer, David, Schwab, Martin E., Gerber, Urs, Ster, Jeanne
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057643/
https://www.ncbi.nlm.nih.gov/pubmed/30040841
http://dx.doi.org/10.1371/journal.pone.0200896
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author Berry, Stewart
Weinmann, Oliver
Fritz, Ann-Kristina
Rust, Ruslan
Wolfer, David
Schwab, Martin E.
Gerber, Urs
Ster, Jeanne
author_facet Berry, Stewart
Weinmann, Oliver
Fritz, Ann-Kristina
Rust, Ruslan
Wolfer, David
Schwab, Martin E.
Gerber, Urs
Ster, Jeanne
author_sort Berry, Stewart
collection PubMed
description Recent investigations of Nogo-A, a well characterized protein inhibitor of neurite outgrowth in the brain, have revealed additional functions including a role in neuropsychiatric disorders such as schizophrenia. Here we examined Nogo-A functions in mouse CA3 hippocampal circuitry. Patch clamp recordings showed that the absence of Nogo-A results in a hyperactive network. In addition, mGlu3 metabotropic glutamate receptors, which exhibit mutations in certain forms of schizophrenia, were downregulated specifically in the CA3 area. Furthermore, Nogo-A(-/-) mice showed disordered theta oscillations with decreased incidence and frequency, similar to those observed in mGlu3(-/-) mice. As disruptions in theta rhythmicity are associated with impaired spatial navigation, we tested mice using modified Morris water maze tasks. Mice lacking Nogo-A exhibited altered search strategies, displaying greater dependence on global as opposed to local reference frames. This link between Nogo-A and mGlu3 receptors may provide new insights into mechanisms underlying schizophrenia.
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spelling pubmed-60576432018-08-06 Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits Berry, Stewart Weinmann, Oliver Fritz, Ann-Kristina Rust, Ruslan Wolfer, David Schwab, Martin E. Gerber, Urs Ster, Jeanne PLoS One Research Article Recent investigations of Nogo-A, a well characterized protein inhibitor of neurite outgrowth in the brain, have revealed additional functions including a role in neuropsychiatric disorders such as schizophrenia. Here we examined Nogo-A functions in mouse CA3 hippocampal circuitry. Patch clamp recordings showed that the absence of Nogo-A results in a hyperactive network. In addition, mGlu3 metabotropic glutamate receptors, which exhibit mutations in certain forms of schizophrenia, were downregulated specifically in the CA3 area. Furthermore, Nogo-A(-/-) mice showed disordered theta oscillations with decreased incidence and frequency, similar to those observed in mGlu3(-/-) mice. As disruptions in theta rhythmicity are associated with impaired spatial navigation, we tested mice using modified Morris water maze tasks. Mice lacking Nogo-A exhibited altered search strategies, displaying greater dependence on global as opposed to local reference frames. This link between Nogo-A and mGlu3 receptors may provide new insights into mechanisms underlying schizophrenia. Public Library of Science 2018-07-24 /pmc/articles/PMC6057643/ /pubmed/30040841 http://dx.doi.org/10.1371/journal.pone.0200896 Text en © 2018 Berry 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 (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Berry, Stewart
Weinmann, Oliver
Fritz, Ann-Kristina
Rust, Ruslan
Wolfer, David
Schwab, Martin E.
Gerber, Urs
Ster, Jeanne
Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits
title Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits
title_full Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits
title_fullStr Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits
title_full_unstemmed Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits
title_short Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits
title_sort loss of nogo-a, encoded by the schizophrenia risk gene rtn4, reduces mglu3 expression and causes hyperexcitability in hippocampal ca3 circuits
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057643/
https://www.ncbi.nlm.nih.gov/pubmed/30040841
http://dx.doi.org/10.1371/journal.pone.0200896
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