Gadd45b knockout mice exhibit selective deficits in hippocampus-dependent long-term memory

Prescott T Leach; Shane G Poplawski; Justin W Kenney; Barbara Hoffman; Dan A Liebermann; Ted Abel; Thomas J Gould

doi:10.1101/lm.024984.111

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Gadd45b knockout mice exhibit selective deficits in hippocampus-dependent long-term memory

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Gadd45b knockout mice exhibit selective deficits in hippocampus-dependent long-term memory

Prescott T Leach, Shane G Poplawski, Justin W Kenney, Barbara Hoffman, Dan A Liebermann, Ted Abel and Thomas J Gould

Learning & memory (Cold Spring Harbor, N.Y.), Vol.19(8), pp.319-324

08/2012

DOI: 10.1101/lm.024984.111

PMCID: PMC3407936

PMID: 22802593

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Abstract

Growth arrest and DNA damage-inducible β ( Gadd45b ) has been shown to be involved in DNA demethylation and may be important for cognitive processes. Gadd45b is abnormally expressed in subjects with autism and psychosis, two disorders associated with cognitive deficits. Furthermore, several high-throughput screens have identified Gadd45b as a candidate plasticity-related gene. However, a direct demonstration of a link between Gadd45b and memory has not been established. The current studies first determined whether expression of the Gadd45 family of genes was affected by contextual fear conditioning. Gadd45b , and to a lesser extent Gadd45g , were up-regulated in the hippocampus following contextual fear conditioning, whereas Gadd45a was not. Next, Gadd45b knockout mice were tested for contextual and cued fear conditioning. Gadd45b knockout mice exhibited a significant deficit in long-term contextual fear conditioning; however, they displayed normal levels of short-term contextual fear conditioning. No differences between Gadd45b knockout and wild-type mice were observed in cued fear conditioning. Because cued fear conditioning is hippocampus independent, while contextual fear conditioning is hippocampus dependent, the current studies suggest that Gadd45b may be important for long-term hippocampus-dependent memory storage. Therefore, Gadd45b may be a novel therapeutic target for the cognitive deficits associated with many neurodevelopmental, neurological, and psychiatric disorders.

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Title: Subtitle: Gadd45b knockout mice exhibit selective deficits in hippocampus-dependent long-term memory
Creators: Prescott T Leach - Department of Psychology, Neuroscience Program, Temple University, Philadelphia, Pennsylvania 19122, USA
Shane G Poplawski - Department of Pharmacology, Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Justin W Kenney - School of Biological Sciences, University of Southampton, Southampton S017 1BJ, United Kingdom
Barbara Hoffman - Temple University School of Medicine, Fels Institute for Cancer Research and Molecular Biology, Philadelphia, Pennsylvania 19140, USA
Dan A Liebermann - Temple University School of Medicine, Fels Institute for Cancer Research and Molecular Biology, Philadelphia, Pennsylvania 19140, USA
Ted Abel - Department of Pharmacology, Department of Biology, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
Thomas J Gould - Department of Psychology, Neuroscience Program, Temple University, Philadelphia, Pennsylvania 19122, USA
Resource Type: Journal article
Publication Details: Learning & memory (Cold Spring Harbor, N.Y.), Vol.19(8), pp.319-324
Publisher: Cold Spring Harbor Laboratory Press
DOI: 10.1101/lm.024984.111
PMID: 22802593
PMCID: PMC3407936
ISSN: 1072-0502
eISSN: 1549-5485
Alternative title: The role of Gadd45b in long-term memory
Language: English
Date published: 08/2012
Academic Unit: Molecular Physiology and Biophysics; Psychiatry; Psychological and Brain Sciences; Iowa Neuroscience Institute; Neuroscience and Pharmacology; Biochemistry and Molecular Biology
Record Identifier: 9984065836802771

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