Open AccessLoss of Nogo-A, encoded by the schizophrenia risk gene Rtn4, reduces mGlu3 expression and causes hyperexcitability in hippocampal CA3 circuits
Author(s) -
Stewart Berry,
Oliver Weinmann,
AnnKristina Fritz,
Ruslan Rust,
David P Wolfer,
Martin E. Schwab,
Urs Gerber,
Jeanne Ster
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0200896
Subject(s) - neuroscience , hippocampal formation , schizophrenia (object oriented programming) , hippocampus , morris water navigation task , glutamate receptor , molecular neuroscience , biology , receptor , psychology , psychiatry , genetics
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.