Acute activation of conserved synaptic signaling pathways in Drosophila melanogaster

Abstract

Studies of memory have identified several memory classifications: declarative, implicit, working, and anesthesia-resistant. One simple classification that may be applied to the array of model systems now used to explore memory is the requirement for de novo gene expression and protein synthesis for the formation of long-term memory (LTM). Short-term memory (STM) appears to require the modification of pre-existing neuronal molecules and is resistant to inhibitors of protein synthesis. These molecules, believed to encode proteins that effect long-lasting neuronal changes likely at the level of the synapse, are manifested behaviorally as memory. Neural activity regulates the cellular decision to synthesize these molecules, yet the identity and function of these molecules are largely unknown. What is known has largely been elucidated by work in mollusks and vertebrates in which procedures have been developed to generate neural activity sufficient to induce long-lasting, protein synthesis-dependent neuronal plasticity. Using these procedures, several key intracellular signaling pathways (Ras/ERK, cAMP/PKA) and important early gene products (arc, zif268, AP1) critical to memory have been identified. Similar procedures are not presently available in Drosophila. Establishing these procedures would greatly enhance the Drosophila model system for identification of plasticity molecules and mechanisms that control their expression. We have explored the potential of conditional Drosophila seizure mutants of comatose and CaP60A mutants for the development of a neural activity generation paradigm capable of (1) inducing long lasting and robust neural activity; (2) acute and persistent activation of the ERK signaling pathway and induction of Drosophila homologs of immediate early genes known to be involved in plasticity; (3) alteration of synaptic localization of fasciclin II, a known effector of synaptic plasticity. Using these mutants, we have established the conservation in insects of a known neural activity regulated signaling pathway shown to be critical to both long term plasticity and memory. Secondly, we have identified a central role for AP1, a classical activity induced gene, in regulating Drosophila neural plasticity. The neural activity paradigm coupled with the identification AP1 dual control of both major branches of long term neuronal change, structural and functional plasticity, provides researchers valuable tools for addressing some the outstanding questions facing the plasticity field today.