Our ability to address memory disorders in humans is impeded by the complexity of mammalian memory circuits and our limited understanding of the basic processes underlying memory storage. Many behaviors and molecular processes of the relatively simple Drosophila memory circuit are conserved in mammals, providing a powerful model for investigating memory consolidation. Elucidating the mechanisms underlying memory consolidation in this animal will therefore be useful for gaining insights that can be applied to te more complex neuroanatomy and conserved cell types of mammalian memory circuits. The mushroom bodies (MBs) in the Drosophila brain are important structures for learning and memory that integrate sensory experiences to regulate behavior much like the mammalian hippocampus. Behavioral studies have suggested that the MBs are modulated by a set of cells known as the dorsal paired medial (DPM) neurons, and these neurons have been shown to be necessary for memory consolidation. The explicit functional connectivity between these two groups of cells is still unknown, however, and the cellular mechanisms underlying the DPM neurons'involvement in memory consolidation have not been characterized. The goal of this proposal is to investigate the functional connection between the DPM neurons and the MBs in order to expand our understanding of the cellular interactions responsible for memory consolidation in Drosophila. The primary obstacle to studying this behavioral circuit is that the DPM neurons are fragile and deeply situated in the brain, and are therefore difficult to access using electrophysiology. This proposal utilizes recent innovations in Drosophila genetics to observe the interactions between the DPM neurons and MBs using live fluorescence imaging. Observing the behavior of this memory circuit using pharmacology ex vivo and after a learning paradigm in vivo will contribute to our understanding of the circuit- and cellular-level strategies that animals use to modulate memory consolidation.
Before preventative and curative measures can be developed to address memory impairments that occur as a consequence of disease or trauma in humans, it is necessary to determine how memory is stored in the brain. Many behaviors and molecular processes in the relatively simple Drosophila memory circuit are comparable to those in mammals, providing researchers with a powerful model for investigating memory mechanisms. Understanding the strategies the brain uses to consolidate memory and recognizing how the system can fail is of urgent importance from a public health standpoint, and this system will provide important insights into these processes.