One fundamental question in memory research is how experiences can be transformed into memory traces that persist over a long time, maybe a lifetime. Memories are encoded into neurons as changes in synaptic transmission efficacy and through structural changes by the addition or pruning of synaptic connections. In the light of constant turnover of proteins in living cells, it is hard to conceive how the plastic changes are consolidated to last for days or even weeks. One hypothesis put forward to explain remote memories is that epigenetic mechanisms could convey persistence of long-lasting storage. We have put this hypothesis to test by genetically manipulating epigenetic factors in neurons that encode a lifetime memory for body size in the Drosophila model system. After eclosion, a Drosophila fly learns and consolidates a memory about its own body size and reach. We have shown that naïve flies do not know their body reach and try to surmount a gap that exceeds their reach by far. However, naïve flies can be trained with zebra-striped patterns to build a wrong body-size memory that seems to last for a lifetime. We could identify a set of 18 neurons per hemisphere, that jointly innervate the protocerebral bridge in the central complex of the brain. These neurons require activation of the transcriptional regulator dCREB2 to establish body-size memory. To perpetuate elevated expression levels of dCREB2 targets, epigenetic mechanisms seem to take action. To address the hypothesis, we initiated a pilot study using RNA-interference (RNAi) mediated knockdown of 61 genes encoding epigenetic factors and chromatin remodelers in the relevant neurons. To date, we have identified 11 candidate genes required for body-size memory formation; however, their role in life-long memory maintenance has not been established yet.
The goal of this project is to extent our analysis on the contribution of epigenetic factors to maintain a lifetime memory. The successful candidate will perform cell-specific, conditional RNAi-mediated knockdowns or CRISPR/Cas9-induced cell-specific conditional knockouts of candidate genes in flies 3 days after training. Behavioral test and histological (LSM) analysis will reveal whether challenging the epigenetic machinery after memory consolidation affects memory maintenance.
Publications relevant to the project
Krause T, Spindler L, Poeck B, Strauss R (2019) Drosophila acquires a long-lasting body-size memory from visual feedback. Curr. Biol. 29(11):1833-1841.e3.
Triphan T, Poeck B, Neuser K, Strauss R (2010) Visual targeting of motor actions in climbing Drosophila. Curr. Biol. 20(7):663-668.
Pick S, Strauss R (2005) Goal-driven behavioral adaptations in gap-climbing Drosophila. Curr. Biol. 15(16):1473-1478.