Egr3, a synaptic activity regulated transcription factor that is essential for learning and memory

Lin Li, Sung Hwan Yun, James Keblesh, Barbara L. Trommer, Huangui Xiong, Jelena Radulovic, Warren G. Tourtellotte*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

93 Scopus citations

Abstract

Learning and memory depend upon poorly defined synaptic and intracellular modifications that occur in activated neurons. Mitogen activated protein kinase-extracellular regulated kinase (MAPK-ERK) signaling and de novo protein synthesis are essential aspects of enduring memory formation, but the precise effector molecules of MAPK-ERK signaling in neurons are not well defined. Early growth response (Egr) transcriptional regulators are examples of MAPK-ERK regulated genes and Egr1 (zif268) has been widely recognized as essential for some aspects of learning and memory. Here we show that Egr3, a transcriptional regulator closely related to Egr1, is essential for normal hippocampal long-term potentiation (LTP) and for hippocampal and amygdala dependent learning and memory. In the absence of Egr3, the defects in learning and memory appear to be independent of Egr1 since Egr1 protein levels are not altered in amygdala, hippocampus or cortex. Moreover, unlike Egr1-deficient mice which have impairments in late phase hippocampal LTP and consolidation of some forms of long-term hippocampus- and amygdala-dependent memory, Egr3-deficient mice have profound defects in early- and late-phase hippocampal LTP, as well as short-term and long-term hippocampus- and amygdala-dependent learning and memory. Thus, Egr3 has an essential role in learning and memory processing that appears to be partly distinct from the role of Egr1.

Original languageEnglish (US)
Pages (from-to)76-88
Number of pages13
JournalMolecular and Cellular Neuroscience
Volume35
Issue number1
DOIs
StatePublished - May 2007

Funding

We thank P. Penzes and R. Huganir for antibody reagents. We thank J. Disterhoft and R. Miller for comments on the manuscript, and members of the Tourtellotte lab for helpful discussion and advice. Technical assistance was provided by J. Whitehead. This study was supported by The National Institutes of Health (NS046468 and NS040748) and a Howard Hughes Faculty Scholar Award to W.G.T.

Keywords

  • Erk
  • Learning
  • MAPK
  • Memory
  • Mouse
  • Plasticity
  • Transcriptional regulation

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience
  • Molecular Biology
  • Cell Biology

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