title: Synapsin determines memory strength after punishment- and relief-learning.
abstract: Adverse life events can induce two kinds of memory with opposite valence, dependent on timing: "negative" memories for stimuli preceding them and "positive" memories for stimuli experienced at the moment of "relief." Such punishment memory and relief memory are found in insects, rats, and man. For example, fruit flies (Drosophila melanogaster) avoid an odor after odor-shock training ("forward conditioning" of the odor), whereas after shock-odor training ("backward conditioning" of the odor) they approach it. Do these timing-dependent associative processes share molecular determinants? We focus on the role of Synapsin, a conserved presynaptic phosphoprotein regulating the balance between the reserve pool and the readily releasable pool of synaptic vesicles. We find that a lack of Synapsin leaves task-relevant sensory and motor faculties unaffected. In contrast, both punishment memory and relief memory scores are reduced. These defects reflect a true lessening of associative memory strength, as distortions in nonassociative processing (e.g., susceptibility to handling, adaptation, habituation, sensitization), discrimination ability, and changes in the time course of coincidence detection can be ruled out as alternative explanations. Reductions in punishment- and relief-memory strength are also observed upon an RNAi-mediated knock-down of Synapsin, and are rescued both by acutely restoring Synapsin and by locally restoring it in the mushroom bodies of mutant flies. Thus, both punishment memory and relief memory require the Synapsin protein and in this sense share genetic and molecular determinants. We note that corresponding molecular commonalities between punishment memory and relief memory in humans would constrain pharmacological attempts to selectively interfere with excessive associative punishment memories, e.g., after traumatic experiences.
authors.affiliation: Leibniz Institut für Neurobiologie (LIN), Abteilung Genetik von Lernen und Gedächtnis, 39118 Magdeburg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Niewalda
authors.affiliation: Leibniz Institut für Neurobiologie (LIN), Abteilung Genetik von Lernen und Gedächtnis, 39118 Magdeburg, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Michels
authors.affiliation: Leibniz Institut für Neurobiologie (LIN), Abteilung Genetik von Lernen und Gedächtnis, 39118 Magdeburg, Germany.
authors.forename: Roswitha
authors.initials: R
authors.lastname: Jungnickel
authors.affiliation: Leibniz Institut für Neurobiologie (LIN), Abteilung Genetik von Lernen und Gedächtnis, 39118 Magdeburg, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Diegelmann
authors.affiliation: Leibniz Institut für Neurobiologie (LIN), Abteilung Genetik von Lernen und Gedächtnis, 39118 Magdeburg, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Kleber
authors.affiliation: Otto von Guericke Universität Magdeburg, Institut für Experimentelle Innere Medizin, 39120 Magdeburg, Germany.
authors.forename: Thilo
authors.initials: T
authors.lastname: Kähne
authors.affiliation: Leibniz Institut für Neurobiologie (LIN), Abteilung Genetik von Lernen und Gedächtnis, 39118 Magdeburg, Germany, Center for Behavioral Brain Sciences (CBBS), 39106 Magdeburg, Germany, and Otto von Guericke Universität Magdeburg, Institut für Biologie, 39106 Magdeburg, Germany bertram.gerber@lin-magdeburg.de.
authors.forename: Bertram
authors.initials: B
authors.lastname: Gerber
mesh_terms: D000367:Age Factors; D000818:Animals; D030801:Animals, Genetically Modified; D001245:Association Learning / Q000502:physiology*; D001362:Avoidance Learning / Q000502:physiology*; D001921:Brain / Q000166:cytology / Q000378:metabolism* / Q000502:physiology; D004192:Discrimination, Psychological; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster; D004597:Electroshock / Q000009:adverse effects; D005260:Female; D008297:Male; D008568:Memory / Q000502:physiology*; D009154:Mutation / Q000235:genetics; D009812:Odorants; D010766:Phosphorylation; D011678:Punishment; D034622:RNA Interference / Q000502:physiology; D016704:Synapsins / Q000235:genetics / Q000502:physiology*
chemical_list: D029721:Drosophila Proteins; D016704:Synapsins
keywords: Drosophila; Synapsin; memory; pain; punishment; relief