A POTENTIAL ROLE FOR CYTOSKELETAL REARRANGEMENT AND FILAMIN 1 DURING LONGTERM MEMORY FORMATION

Objectives: Filamin 1 defects underlie periventricular nodular heterotopia, an inherited form of cerebral malformation with cognitive dysfunction. We are investigating a more direct link between Filamin 1 function and memory formation per se.

Methods: From a behavioural screen for gene mutations that affect one-day memory formation, we identified the joy mutant strain, flies from which carry molecular lesions of the Filamin 1 gene. We also have performed gene expression studies in normal flies using DNA microarry technology to identify genes involved in transcription-dependent long-term memory. RNA was extracted from 10 replicate samples of fly heads for each training protocol. Corresponding DNA probes from these RNA extracts then were hybridized to a total of 20 Affymetrix gene expression microarrays. Statistical analysis of the treatment effect yielded more than 4500 candidate memory genes (CMGs). Among these CMGs are known genes involved in the Filamin 1 pathway, as established in various models and contexts.

Results: We found that 23 CMGs were included among the 62 known Filamin 1 pathway genes. Further molecular and behavioural experiments are underway to provide in vivo validation of these CMGs.

Conclusion: Considering the role of Filamin 1 in cell-cell contact and cell-morphology, two phenomenons observed in long-term memory formation, we have investigated a putative role for the Filamin 1 pathway. Our study of Drosophila mutants suggests a role for Filamin 1 during long-term memory formation. In addition, a subset of Filamin 1 pathway component genes shows significant transcriptional regulation in normal flies during long-term memory formation. Further validation will involve genetic complementation, transgenic rescue and quantitative PCR. Finally, similar behaviour measure with temporally regulated expression on Filamin 1 will allow to identifying the developmental contribution of Filamin 1 to long-term memory and synaptic plasticity.