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      Impaired Long-Term Memory and NR2A-Type NMDA Receptor-Dependent Synaptic Plasticity in Mice Lacking c-Fos in the CNS

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          Abstract

          The immediate early gene c- fos is part of the activator protein-1 transcription factor and has been postulated to participate in the molecular mechanisms of learning and memory. To test this hypothesis in vivo, we generated mice with a nervous system-specific c- fos knock-out using the Cre-loxP system. Adult mice lacking c-Fos in the CNS (c- fos ΔCNS) showed normal general and emotional behavior but were specifically impaired in hippocampus-dependent spatial and associative learning tasks. These learning deficits correlated with a reduction of long-term potentiation (LTP) in hippocampal CA3-CA1 synapses. The magnitude of LTP was restored by a repeated tetanization procedure, suggesting impaired LTP induction in c- fos ΔCNS mice. This rescue was blocked by a selective inhibitor of NR2B-type NMDA receptors. This blockade was compensated in wild-type mice by NR2A-type NMDA receptor-activated signaling pathways, thus indicating that these pathways are compromised in c- fos ΔCNS mice. In summary, our data suggest a role for c-Fos in hippocampus-dependent learning and memory as well as in NMDA receptor-dependent LTP formation.

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          Author and article information

          Journal
          J Neurosci
          J. Neurosci
          jneuro
          The Journal of Neuroscience
          Society for Neuroscience
          0270-6474
          1529-2401
          8 October 2003
          : 23
          : 27
          : 9116-9122
          Affiliations
          [1 ]Research Institute of Molecular Pathology, 1030 Vienna, Austria, [2 ]Institute of Basic Medical Sciences, University of Oslo, N-0317 Oslo, Norway, [3 ]Central Institute of Mental Health, D-68159 Mannheim, Germany, and [4 ]Max Planck Institute for Medical Research, D-69120 Heidelberg, Germany
          Article
          PMC6740829 PMC6740829 6740829 0239116
          10.1523/JNEUROSCI.23-27-09116.2003
          6740829
          14534245
          2652733d-5b69-4e1b-8ac5-b85d9f4e758c
          Copyright © 2003 Society for Neuroscience 0270-6474/03/239116-07.00/0
          Categories
          Cellular/Molecular
          Custom metadata
          9116
          ARTICLE

          hippocampus,behavior,mice,long-term potentiation,NMDA receptor,conditional,c-fos

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