Presynaptic plasticity in the control of mushroom body memory formation

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There is still a fundamental gap in our understanding of how dynamic changes of synapse performance (“plasticity”) intersect with circuit operation and, consequently, define behavioral states. The Drosophila mushroom body (MB) offers for an integrated analysis connecting the molecular/cellular with the behavioral level, here aversive olfactory memory formation and consolidation. We in the last funding period analyzed the role of homeostatic presynaptic plasticity (“PreScale”) for memory formation in the MB Kenyon cells (KCs), a plasticity form we previously found responsible to structurally/functionally remodel presynaptic active zones over 10s of minutes. We found that KC-specific post-developmental knockdown of executory synaptic and regulatory proteins driving PreScale did not affect short-term memory, but robustly interfered with the retrieval of mid-term memories. Still, we still lack an understanding of the spatio-temporal action of this plasticity form within the MB circuitry. We now suggest to reduce the cellular and behavioral complexity of our analysis by restricting the KC neuron subsets analyzed and involve simple learning strategies. Moreover, we strive to directly visualize the plasticity processes taken place at KC synapses, and in connection extend our knowledge concerning the molecular/cell-biological machinery orchestrating PreScale. In result, we hope to arrive at a picture of how circuit refinement uses homeostatic plasticity to allow for the successful circuit integration of to be learned information along the consolidation trajectory.