Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits
Schwab, Martin E.
- Journal Article
Rechte / LizenzCreative Commons Attribution 4.0 International
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. Mehr anzeigen
Zeitschrift / SeriePLoS ONE
Seiten / Artikelnummer
VerlagPublic Library of Science
Organisationseinheit03727 - Wolfer, David P. / Wolfer, David P.