%0 Journal Article %A Kenneth J. O’Riordan %A I-Chia Huang %A Marina Pizzi %A PierFranco Spano %A Flora Boroni %A Regula Egli %A Priyanka Desai %A Olivia Fitch %A Lauren Malone %A Hyung Jin Ahn %A Hsiou-Chi Liou %A J. David Sweatt %A Jonathan M. Levenson %T Regulation of Nuclear Factor κB in the Hippocampus by Group I Metabotropic Glutamate Receptors %D 2006 %R 10.1523/JNEUROSCI.4527-05.2006 %J The Journal of Neuroscience %P 4870-4879 %V 26 %N 18 %X An increasing amount of evidence suggests that the family of nuclear factor κB (NF-κB) transcription factors plays an important role in synaptic plasticity and long-term memory formation. The present study investigated the regulation of NF-κB family members p50, p65/RelA, and c-Rel in the hippocampus in response to metabotropic glutamate receptor (mGluR) signaling. Activation of group I metabotropic glutamate receptors (GpI-mGluRs) with the agonist (S)-3,5-dihydroxyphenylglycine (DHPG) resulted in a time-dependent increase in DNA binding activity of p50, p65, and c-Rel in area CA1 of the hippocampus. An antagonist of mGluR5, 2-Methyl-6-(phenylethynyl)pyridine, inhibited the DHPG-induced activation of NF-κB, whereas an antagonist of mGluR1, (S)-(+)-α-amino-4-carboxy-2-methylbenzeneacetic acid, did not. Using a series of inhibitors, we investigated the signaling pathways necessary for DHPG-induced activation of NF-κB and found that they included the phosphatidyl inositol 3-kinase, protein kinase C, mitogen-activated protein kinase kinase, and p38-mitogen-activated protein kinase pathways. To determine the functional significance of mGluR-induced regulation of NF-κB, we measured long-term depression (LTD) of Schaffer-collateral synapses in the hippocampus of c-Rel knock-out mice. Early phase LTD was normal in c-rel−/− mice. However, late-phase LTD (>90 min) was impaired in c-rel−/− mice. The observations of this deficit in hippocampal synaptic plasticity prompted us to further investigate long-term memory formation in c-rel−/− mice. c-rel−/− mice exhibited impaired performance in a long-term passive avoidance task, providing additional evidence for c-Rel in long-term memory formation. These results demonstrate that the NF-κB transcription factor family is regulated by GpI-mGluRs in the hippocampus and that the c-Rel transcription factor is necessary for long-term maintenance of LTD and formation of long-term memory. %U https://www.jneurosci.org/content/jneuro/26/18/4870.full.pdf