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

Furthermore, a one-way ANOVA revealed a highly significant difference among cue conditions on Nogo-A -/- animals when examining all probe trials from all animals used in both mazes (F(2,95) = 7.173, P = < 0.001).

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The frequency of theta oscillations and theta episodes in response to application of LCCG-I (10 μM), a group II mGlu receptor agonist, was reduced significantly in Nogo-A -/- and showed a trend towards reduction in mGlu3 -/- hippocampal slices as compared to wild type (frequency: WT = 13.9 ± 0.8 Hz, Nogo-A -/- = 11.4 ± 0.7 Hz, mGlu3 -/- = 10.7 ± 0.6 Hz, P (WT-Nogo-A -/- ) = 0.034, P (WT- mGlu3 -/- ) = 0.008; episodes/min: WT = 17.2 ± 2.8, Nogo-A -/- = 7.0 ± 2.0, mGlu3 -/- = 12.3 ± 2.7; P (WT-Nogo-A -/- ) = 0.011, P (WT- mGlu3 -/- ) = 0.241; Fig 5B ).

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