Inducible Enhancement of Memory Storage and Synaptic Plasticity in Transgenic Mice Expressing an Inhibitor of ATF4 (CREB-2) and C/EBP Proteins

Amy Chen; Isabel A Muzzio; Gaël Malleret; Dusan Bartsch; Miguel Verbitsky; Paul Pavlidis; Amanda L Yonan; Svetlana Vronskaya; Michael B Grody; Ivan Cepeda; T.Conrad Gilliam; Eric R Kandel

doi:10.1016/S0896-6273(03)00501-4

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Inducible Enhancement of Memory Storage and Synaptic Plasticity in Transgenic Mice Expressing an Inhibitor of ATF4 (CREB-2) and C/EBP Proteins

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Inducible Enhancement of Memory Storage and Synaptic Plasticity in Transgenic Mice Expressing an Inhibitor of ATF4 (CREB-2) and C/EBP Proteins

Amy Chen, Isabel A Muzzio, Gaël Malleret, Dusan Bartsch, Miguel Verbitsky, Paul Pavlidis, Amanda L Yonan, Svetlana Vronskaya, Michael B Grody, Ivan Cepeda, …

Neuron (Cambridge, Mass.), Vol.39(4), pp.655-669

2003

DOI: 10.1016/S0896-6273(03)00501-4

PMID: 12925279

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Abstract

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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Title: Subtitle: Inducible Enhancement of Memory Storage and Synaptic Plasticity in Transgenic Mice Expressing an Inhibitor of ATF4 (CREB-2) and C/EBP Proteins
Creators: Amy Chen - Columbia University
Isabel A Muzzio - Columbia University
Gaël Malleret - Columbia University
Dusan Bartsch - Columbia University
Miguel Verbitsky - Columbia University
Paul Pavlidis - Columbia University
Amanda L Yonan - Columbia University
Svetlana Vronskaya - Columbia University
Michael B Grody - Columbia University
Ivan Cepeda - Columbia University
T.Conrad Gilliam - Columbia University
Eric R Kandel - Columbia University
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.39(4), pp.655-669
DOI: 10.1016/S0896-6273(03)00501-4
PMID: 12925279
NLM abbreviation: Neuron
ISSN: 0896-6273
eISSN: 1097-4199
Publisher: Elsevier Inc
Language: English
Date published: 2003
Academic Unit: Psychological and Brain Sciences; Iowa Neuroscience Institute
Record Identifier: 9984295023302771

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