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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...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2018
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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. |
format | Online Article Text |
id | pubmed-6057643 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
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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