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Publication : Inducible enhancement of memory storage and synaptic plasticity in transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP proteins.

First Author  Chen A Year  2003
Journal  Neuron Volume  39
Issue  4 Pages  655-69
PubMed ID  12925279 Mgi Jnum  J:85101
Mgi Id  MGI:2671714 Doi  10.1016/s0896-6273(03)00501-4
Citation  Chen A, et al. (2003) Inducible enhancement of memory storage and synaptic plasticity in transgenic mice expressing an inhibitor of ATF4 (CREB-2) and C/EBP proteins. Neuron 39(4):655-69
abstractText  To examine the role of C/EBP-related transcription factors in long-term synaptic plasticity and memory storage, we have used the tetracycline-regulated system and expressed in the forebrain of mice a broad dominant-negative inhibitor of C/EBP (EGFP-AZIP), which preferentially interacts with several inhibiting isoforms of C/EBP. EGFP-AZIP also reduces the expression of ATF4, a distant member of the C/EBP family of transcription factors that is homologous to the Aplysia memory suppressor gene ApCREB-2. Consistent with the removal of inhibitory constraints on transcription, we find an increase in the pattern of gene transcripts in the hippocampus of EGFP-AZIP transgenic mice and both a reversibly enhanced hippocampal-based spatial memory and LTP. These results suggest that several proteins within the C/EBP family including ATF4 (CREB-2) act to constrain long-term synaptic changes and memory formation. Relief of this inhibition lowers the threshold for hippocampal-dependent long-term synaptic potentiation and memory storage in mice.
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