Recently a study from Ryszard Maleszka’s Lab demonstrates that DNA methylation does play a role in the acquisition of memory and mediates the resistance of this memory to extinction in honeybees (Lockett et al 2010). Now the group of Paul Szyszka in Konstanz provides additional information about the role of DNA methylation in the formation of long term memory.
Using olfactory conditioning of the proboscis extension response (PER), Stephanie Biergans et al. were able to show that DNA methylation mediates the specificity of long term memory, but not short term memory. They trained bees with three odor (conditioned stimulus = CS) – sugar (unconditioned stimulus = US) trials. During this acquisition phase they applied an inhibitor of DNA methylation, Zebularine (blocker of DNA methyltransferase). The bees were tested at different time points afterwards (30 min, 1 day or 3 days) with the trained odor and with an untrained odor. The results show that there is no effect of the inhibitor on the CS memory tests (neither on short term at 30 min nor on long term memory at 1 d or 3 d), traceably the authors conclude that the memory strength is not altered by Zebularin. Nevertheless the data demonstrates that the long term memory is less specific. The specificity was measured as a discrimination index for each bee, calculated as the difference of CS response (1 = PER in test or 0 = no PER) minus the response to an untrained odor (1 = PER in test or 0 = no PER). S. Biergans et al show that these indexes are reduced in Zebularine treated bees compared to bees treated with the vehicle. In other words Zebularine treatment increases the response to the untrained odor; even though this is not exactly what the authors were checking for. In well thought control experiments the people from Konstanz show that the perception of odors in itself is not altered by the drug and importantly that Zebularine does not affect the survival of the bees. Taken these results together the authors suggest that “…different genetic pathways are involved in mediating the strength and discriminatory power of associative odor memories…” (discriminatory power as an elegant synonym for specificity). The question left open (for me) is whether the drug just makes the memory more fuzzy and consequently increases generalization or if there is some other component, for example a non associative component mediated by the US, which is down regulated via DNA methylation during CS-US learning.
Anyway the nice study from Paul Szyszka’s group does not only increase the knowledge about the role of epigenetic mechanism in memory formation, it also highlights the major fact that stimulus specificity is an important issue in investigations concerning the molecular basis of memory formation.
Biergans SD, Jones JC, Treiber N, Galizia CG, & Szyszka P (2012). DNA methylation mediates the discriminatory power of associative long-term memory in honeybees. PloS one, 7 (6) PMID: 22724000
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