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NF-kB functions in synaptic signaling and behavior

Meffert, Mollie K. and Chang, Jolene M. and Wiltgen, Brian J. and Fanselow, Michael S. and Baltimore, David (2003) NF-kB functions in synaptic signaling and behavior. Nature Neuroscience, 6 (10). pp. 1072-1078. ISSN 1097-6256. https://resolver.caltech.edu/CaltechAUTHORS:20150409-082723140

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Abstract

Ca^(2+)-regulated gene transcription is essential to diverse physiological processes, including the adaptive plasticity associated with learning. We found that basal synaptic input activates the NF-kB transcription factor by a pathway requiring the Ca^(2+)/calmodulin-dependent kinase CaMKII and local submembranous Ca^(2+) elevation. The p65:p50 NF-kB form is selectively localized at synapses; p65-deficient mice have no detectable synaptic NF-kB. Activated NF-kB moves to the nucleus and could directly transmute synaptic signals into altered gene expression. Mice lacking p65 show a selective learning deficit in the spatial version of the radial arm maze. These observations suggest that long-term changes to adult neuronal function caused by synaptic stimulation can be regulated by NF-kB nuclear translocation and gene activation.


Item Type:Article
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http://dx.doi.org/10.1038/nn1110 DOIArticle
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ORCID:
AuthorORCID
Baltimore, David0000-0001-8723-8190
Additional Information:© 2003 Nature Publishing Group. Received 2 June 2003; Accepted 24 June 2003; Published online: 31 August 2003. We thank E. Schuman and U. Bayer for support, discussion and critical reading of the manuscript, H. Schulman and his laboratory for the antCNt peptide, and E. Brown, A. Hoffman, J. Pomerantz and other members of the D. Baltimore laboratory for support and suggestions. We thank E. Alcamo for creating the double-knockout mouse line TNFR1/p65, which was critical to our experiments, and M. Sanders for training and assistance with behavioral assays. This work was supported by a National Institute of Neurological Disorders and Stroke (NINDS) KO8 grant to M.K.M. and a National Institutes of Health (NIH) grant to D.B.
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Funding AgencyGrant Number
National Institute of Neurological Disorders and Stroke (NINDS)UNSPECIFIED
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Issue or Number:10
Record Number:CaltechAUTHORS:20150409-082723140
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20150409-082723140
Official Citation:Meffert, M., Chang, J., Wiltgen, B. et al. NF-κB functions in synaptic signaling and behavior. Nat Neurosci 6, 1072–1078 (2003). https://doi.org/10.1038/nn1110
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ID Code:56506
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:09 Apr 2015 19:13
Last Modified:17 Apr 2020 19:50

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