Journal
JOURNAL OF NEUROSCIENCE
Volume 32, Issue 48, Pages 17059-17066Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.1747-12.2012
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Funding
- NIH [MH095270, MH57014, AG031722, NS057098, P30 NS47466]
- Ellison Medical Foundation
- McKnight Brain Research Foundation
- University of Alabama at Birmingham Neuroscience Molecular Detection Core
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Dynamic epigenetic mechanisms including histone and DNA modifications regulate animal behavior and memory. While numerous enzymes regulating these mechanisms have been linked to memory formation, the regulation of active DNA demethylation (i.e., cytosine-5 demethylation) has only recently been investigated. New discoveries aim toward the Growth arrest and DNA damage-inducible 45 (Gadd45) family, particularly Gadd45b, in activity-dependent demethylation in the adult CNS. This study found memory-associated expression of gadd45b in the hippocampus and characterized the behavioral phenotype of gadd45(b-/-) mice. Results indicate normal baseline behaviors and initial learning but enhanced persisting memory in mutants in tasks of motor performance, aversive conditioning and spatial navigation. Furthermore, we showed facilitation of hippocampal long-term potentiation in mutants. These results implicate Gadd45b as a learning-induced gene and a regulator of memory formation and are consistent with its potential role in active DNA demethylation in memory.
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