CORDIS

Drosophila is a valuable model organism in the discovery of new memory genes because of the simplicity of its brain and the power of its genetics. Drosophila can store memories for more than 24 hours - a process known as long-term memory (LTM) (4,5). LTM seems to be evolutionarily conserved since similar genes such as the transcription factor CREB play an important role in this process in as diverse animals as snails, flies and mice (1,3). Transcription factors have been long known to play an important role in LTM (1). However, until now, only a few of them have been identified and studied in this process until now. Here, we propose to use Drosophila to identify and characterize new transcription factors involved in LTM. We will use micro-arrays to compare t he expression profiles of LTM trained and untrained flies. Transcription factors with modified expression profiles will be tested directly for their involvement in LTM in vivo: UAS-RNAi constructs for the particular transcription factors will be expressed in the adult fly brain in a temporally and spatially controlled manner using conditional-GAL4 drivers, and these flies will be tested for LTM performance. One/few transcription factors will be selected to be further analysed in detail for their specific role in the olfactory LTM formation.

The expression patterns will be examined by stainings, the particular regulatory pathways will be delineated using fly genetics, and the putative interactors or target promoters will be characterized using biochemistry and molecular biology methods. Given the evolutionary conservation of the molecular mechanisms of neuronal plasticity, the characterization of new LTM transcription factors in Drosophila may help even to understand how human memories are stored and shed light on the genetic background of certain memory disorders.