title: The histone deacetylase HDAC4 regulates long-term memory in Drosophila.
abstract: A growing body of research indicates that pharmacological inhibition of histone deacetylases (HDACs) correlates with enhancement of long-term memory and current research is concentrated on determining the roles that individual HDACs play in cognitive function. Here, we investigate the role of HDAC4 in long-term memory formation in Drosophila. We show that overexpression of HDAC4 in the adult mushroom body, an important structure for memory formation, resulted in a specific impairment in long-term courtship memory, but had no affect on short-term memory. Overexpression of an HDAC4 catalytic mutant also abolished LTM, suggesting a mode of action independent of catalytic activity. We found that overexpression of HDAC4 resulted in a redistribution of the transcription factor MEF2 from a relatively uniform distribution through the nucleus into punctate nuclear bodies, where it colocalized with HDAC4. As MEF2 has also been implicated in regulation of long-term memory, these data suggest that the repressive effects of HDAC4 on long-term memory may be through interaction with MEF2. In the same genetic background, we also found that RNAi-mediated knockdown of HDAC4 impairs long-term memory, therefore we demonstrate that HDAC4 is not only a repressor of long-term memory, but also modulates normal memory formation.
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Helen L
authors.initials: HL
authors.lastname: Fitzsimons
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Silvia
authors.initials: S
authors.lastname: Schwartz
authors.affiliation: Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.
authors.forename: Fiona M
authors.initials: FM
authors.lastname: Given
authors.affiliation: Department of Entomology, North Carolina State University, Raleigh, North Carolina, United States of America.
authors.forename: Maxwell J
authors.initials: MJ
authors.lastname: Scott
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006655:Histone Deacetylases / Q000096:biosynthesis* / Q000235:genetics; D057567:Memory, Long-Term / Q000502:physiology*; D024521:Mushroom Bodies / Q000166:cytology / Q000201:enzymology*; D018006:Myogenic Regulatory Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D029721:Drosophila Proteins; C499409:Mef2 protein, Drosophila; D018006:Myogenic Regulatory Factors; C559672:HDAC4 protein, Drosophila; D006655:Histone Deacetylases