dCREB2-mediated enhancement of memory formation

J Neurosci. 2013 Apr 24;33(17):7475-87. doi: 10.1523/JNEUROSCI.4387-12.2013.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Animals, Genetically Modified
  • Cell Line
  • Cyclic AMP Response Element-Binding Protein / genetics
  • Cyclic AMP Response Element-Binding Protein / physiology*
  • Drosophila
  • Drosophila Proteins / genetics
  • Drosophila Proteins / physiology*
  • Memory, Long-Term / physiology*
  • Molecular Sequence Data
  • Trans-Activators / genetics
  • Trans-Activators / physiology*


  • CrebB protein, Drosophila
  • Cyclic AMP Response Element-Binding Protein
  • Drosophila Proteins
  • Trans-Activators