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

Leach, Prescott T., Poplawski, Shane G., Kenney, Justin W., Hoffman, Barbara, Liebermann, Dan A., Abel, Ted and Gould, Thomas J. (2012) Gadd45b knockout mice exhibit selective deficits in hippocampus-dependent long-term memory Learning & Memory, 19, (8), pp. 319-324. (doi:10.1101/lm.024984.111). (PMID:22802593).

Record type: Article

Abstract

Growth arrest and DNA damage-inducible ? (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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e-pub ahead of print date: 16 July 2012
Published date: August 2012
Organisations: Molecular and Cellular

Identifiers

Local EPrints ID: 343514
URI: http://eprints.soton.ac.uk/id/eprint/343514
ISSN: 1072-0502
PURE UUID: 50d5bf69-0eb0-4e58-8ed0-61f0acd4a0cc

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Date deposited: 08 Oct 2012 12:00
Last modified: 18 Jul 2017 05:22

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Contributors

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

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