Mechanisms of compartmentalized plasticity in learning and memory

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Project Summary A major goal of neuroscience research is to understand how experience reweights the flow of information across brain circuits. This involves plasticity that occurs at across different regions of neurons (i.e., subcellular compartmentalization). Our preliminary data revealed compartmentalization of signaling within neurons that encode olfactory memories, and further found that learning drives spatially broad elevations of Ca2+. This suggests that multiple signals are integrated across different spatial scales during learning events to modulate compartmentalized plasticity. Here we will test how compartmentalized plasticity drives the ensembles of changes across multiple spatial scales in the nervous system that leads to coherent action selection. We will test the mechanisms of compartmentalized presynaptic plasticity down to the subcellular level, using the genetically powerful, highly tractable nervous system of Drosophila melanogaster. The Drosophila mushroom body (MB) carries olfactory information from olfactory projection neurons to downstream circuits that mediate fundamental decision-making processes. We will use this system as a testbed to dissect the mechanisms of compartmentalized plasticity at the molecular levels, examine cellular integration and synaptic plasticity, and probe how these processes modulate behavioral action selection via actions on discrete circuits that modulate behavior. Understanding how memories are encoded in the brain and disrupted in brain disorders is a prerequisite to the rational design of treatments for memory impairment. Results of the present studies will provide guideposts for future research into the molecular biology of memory formation across multiple model organisms (including mammals), as the function of key molecules, cellular mechanisms, cellular compartmentalization and synaptic function, circuit motifs, and computational primitives are both conserved across species and crucial across multiple circuits & types of memory. The project will support our long-term goal of understanding of memory down to the single-cell level, contributing to the knowledge base necessary for the rational development of novel treatments for memory impairment.