title: Enhanced memory persistence is blocked by a DNA methyltransferase inhibitor in the snail Lymnaea stagnalis.
abstract: Lymnaea stagnalis provides an excellent model system for studying memory because these snails have a well-described set of neurons, a single one of which controls expression of long-term memory of operantly conditioned respiratory behavior. We have shown that several different manipulations, including pre-training exposure to serotonin (5-HT) or methamphetamine, submersion of snails after training to prevent memory interference, and exposure to effluent from predatory crayfish (CE), enhance memory persistence. Changes in DNA methylation underlie formation of strong memories in mammals and 5-HT-enhanced long-term facilitation in Aplysia. Here we determined the impact of the DNA methyltransferase inhibitor, 5-aza-2'-deoxycytidine (5-AZA; 87 μmol l(-1)), on enhanced memory persistence by all four manipulations. We found that 5-HT (100 μmol l(-1)) enhanced memory persistence, which was blocked by 5-AZA pretreatment. Snails pre-exposed to 3.3 μmol l(-1) Meth 4 h prior to training demonstrated memory 72 h later, which was not present in controls. This memory-enhancing effect was blocked by pre-treatment with 87 μmol l(-1) 5-AZA. Similarly, submersion to prevent interference learning as well as training in CE produced memory that was not present in controls, and these effects were blocked by pre-treatment with 87 μmol l(-1) 5-AZA. In contrast, 5-AZA injection did not alter expression of normal (non-enhanced) memory, suggesting that these four stimuli enhance memory persistence by increasing DNA methyltransferase activity, which, in turn, increases expression of memory-enhancing genes and/or inhibits memory suppressor genes. These studies lay important groundwork for delineating gene methylation changes that are common to persistent memory produced by different stimuli.
authors.affiliation: Cumming School of Medicine, University of Calgary, Calgary, AL T2N 4N1, Canada.
authors.forename: Ken
authors.initials: K
authors.lastname: Lukowiak
authors.affiliation: Alcohol and Drug Abuse Research Program and Translational Addiction Research Center, Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA 98686, USA.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Heckler
authors.affiliation: Alcohol and Drug Abuse Research Program and Translational Addiction Research Center, Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA 98686, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Bennett
authors.affiliation: Alcohol and Drug Abuse Research Program and Translational Addiction Research Center, Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA 98686, USA.
authors.forename: Ellen K
authors.initials: EK
authors.lastname: Schriner
authors.affiliation: Alcohol and Drug Abuse Research Program and Translational Addiction Research Center, Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA 98686, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Wyrick
authors.affiliation: Alcohol and Drug Abuse Research Program and Translational Addiction Research Center, Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA 98686, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Jewett
authors.affiliation: Alcohol and Drug Abuse Research Program and Translational Addiction Research Center, Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA 98686, USA.
authors.forename: Ryan P
authors.initials: RP
authors.lastname: Todd
authors.affiliation: Alcohol and Drug Abuse Research Program and Translational Addiction Research Center, Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA 98686, USA sorg@vetmed.wsu.edu.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Sorg
mesh_terms: D000818:Animals; D003400:Astacoidea / Q000737:chemistry; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019175:DNA Methylation / Q000187:drug effects; D015254:DNA Modification Methylases / Q000037:antagonists & inhibitors*; D000077209:Decitabine; D007101:Immersion; D008195:Lymnaea / Q000502:physiology*; D057567:Memory, Long-Term / Q000187:drug effects*; D008694:Methamphetamine / Q000494:pharmacology; D009812:Odorants / Q000032:analysis; D012701:Serotonin / Q000494:pharmacology
chemical_list: D012701:Serotonin; D008694:Methamphetamine; D000077209:Decitabine; D015254:DNA Modification Methylases; D001374:Azacitidine
keywords: DNA methylation; Epigenetics; Forgetting; Long-term memory; Methamphetamine; Snail