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Updated: Feb 7, 2026

Measurement of Fronto-limbic Activity Using an Emotional Oddball Task in Children with Familial High Risk for Schizophrenia
Published on: December 2, 2015
Loss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in
Stewart Berry1, Oliver Weinmann1, Ann-Kristina Fritz2
1Brain Research Institute, University of Zurich, Zurich, Switzerland.
Abstract:
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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