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Updated: May 12, 2026

Aversive Associative Learning and Memory Formation by Pairing Two Chemicals in Caenorhabditis elegans
Published on: June 23, 2022
dCREB2-mediated enhancement of memory formation
Thomas C Tubon1, Jiabin Zhang, Eugenia L Friedman
1Department of Genetics and Neurology, Institute on Aging, Neuroscience Training Program, Wisconsin Institute of Medical Research, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
Abstract:
CREB-responsive transcription has an important role in adaptive responses in all cells and tissue. In the nervous system, it has an essential and well established role in long-term memory formation throughout a diverse set of organisms. Activation of this transcription factor correlates with long-term memory formation and disruption of its activity interferes with this process. Most convincingly, augmenting CREB activity in a number of different systems enhances memory formation. In Drosophila, a sequence rearrangement in the original transgene used to enhance memory formation has been a source of confusion. This rearrangement prematurely terminates translation of the full-length protein, leaving the identity of the "enhancing molecule" unclear. In this report, we show that a naturally occurring, downstream, in-frame initiation codon is used to make a dCREB2 protein off of both transgenic and chromosomal substrates. This protein is a transcriptional activator and is responsible for memory enhancement. A number of parameters can affect enhancement, including the short-lived activity of the activator protein, and the time-of-day when induction and behavioral training occur. Our results reaffirm that overexpression of a dCREB2 activator can enhance memory formation and illustrate the complexity of this behavioral enhancement.
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