The long-term goals of this research project are to elucidate the nature of cellular memory traces, the mechanisms underlying their formation, their duration, and the neurons in which they form within the Drosophila olfactory nervous system. Recent advances in optical imaging of neural activity in specific neurons of the fly's brain have allowed for the visualization of an olfactory memory trace for the first time. Experiments that will extend these observations are proposed. The complete representation of odors by neural activity in the antennal lobe will be elucidated along with the changes in this representation that occur with conditioning. The mechanisms underlying these changes in representation, or memory traces, will be probed using mutants and the expression of functionally inactivating transgenes. The naive and conditioned odorant responses that occur within other neurons of the olfactory nervous system, including the DPM and mushroom body neurons, will be studied using these same optical imaging techniques. The proposed experiments will detect these memory traces, and provide knowledge about their persistence and their specificity to conditioned odors. The mechanisms underlying the formation of DPM and mushroom body neuron memory traces will also be probed using mutants and functionally inactivating transgenes. The hypothesis that dopaminergic neurons convey the unconditioned stimulus to mushroom body neurons will be tested by examining dopaminergic responses to unconditioned and conditioned stimuli. Finally, comparisons will be made between the cellular memory traces that form in the olfactory nervous system using aversive unconditioned stimuli and appetitive unconditioned stimuli with the same odor conditioned stimulus. These experiments will significantly increase our understanding of how memories form and the events that can potentially perturb normal memory formation. This will aid in our understanding of the diseases that affect memory formation.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Mamounas, Laura
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Scripps Research Institute
La Jolla
United States
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Yu, Dinghui; Tan, Ying; Chakraborty, Molee et al. (2018) Elongator complex is required for long-term olfactory memory formation in Drosophila. Learn Mem 25:183-196
Berry, Jacob A; Phan, Anna; Davis, Ronald L (2018) Dopamine Neurons Mediate Learning and Forgetting through Bidirectional Modulation of a Memory Trace. Cell Rep 25:651-662.e5
Himmelreich, Sophie; Masuho, Ikuo; Berry, Jacob A et al. (2017) Dopamine Receptor DAMB Signals via Gq to Mediate Forgetting in Drosophila. Cell Rep 21:2074-2081
Cervantes-Sandoval, Isaac; Phan, Anna; Chakraborty, Molee et al. (2017) Reciprocal synapses between mushroom body and dopamine neurons form a positive feedback loop required for learning. Elife 6:
Davis, Ronald L; Zhong, Yi (2017) The Biology of Forgetting-A Perspective. Neuron 95:490-503
Drago, Ilaria; Davis, Ronald L (2016) Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila. Cell Rep 16:2763-2776
Cervantes-Sandoval, Isaac; Chakraborty, Molee; MacMullen, Courtney et al. (2016) Scribble Scaffolds a Signalosome for Active Forgetting. Neuron 90:1230-1242
Guven-Ozkan, Tugba; Busto, Germain U; Schutte, Soleil S et al. (2016) MiR-980 Is a Memory Suppressor MicroRNA that Regulates the Autism-Susceptibility Gene A2bp1. Cell Rep 14:1698-1709
Davis, Ronald L (2015) SnapShot: Olfactory Classical Conditioning of Drosophila. Cell 163:524-524.e1
Berry, Jacob A; Cervantes-Sandoval, Isaac; Chakraborty, Molee et al. (2015) Sleep Facilitates Memory by Blocking Dopamine Neuron-Mediated Forgetting. Cell 161:1656-67

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