The goal of this research is to define the molecular, cellular, and systems neuroscience that provides the basis for active forgetting. This area of learning and memory research has been overlooked and yet, there is every reason to believe that the processes underlying active forgetting are as complicated and important as learning itself and the stabilization of memories by consolidation. The research project utilizes the model system Drosophila melanogaster because of the ease with which the fly can be conditioned using olfactory cues, the numerous genetic and molecular tools available, and the ability to peer into the brain of living animals and watch the activity of different sets of neurons. The latter approach, functional cellular imaging, employs flies carrying transgenes that express reporters for calcium influx, synaptic transmission, or other neuronal events, to monitor changes in neuronal response properties among the expressing neurons before and after conditioning. Our prior studies using this technique demonstrated that dopamine neurons exhibit ongoing activity after the learning event itself and that this activity likely provides a """"""""forgetting"""""""" signal to the postsynaptic mushroom body neurons. We will extend these studies in several different ways to help understand the mechanistic basis for active forgetting. There is a rich medical importance to this research given the well- documented problems of cognition associated with numerous neuropsychiatric disorders.

Public Health Relevance

Memory problems are associated with numerous neuropsychiatric disorders. Despite intensive efforts, a clear understanding of the various processes that lead to stable memories remain unknown. One aspect of learning and memory - that of active forgetting - has remained particularly mysterious. This project will study active forgetting using the experimental model Drosophila melanogaster - because of the ease of studying memory formation in this organism, the ability to peer into its brain and watch the activity of neurons during learning, and the ability to manipulate the activity of defined sets of neurons at will. The knowledge obtained from these studies will contribute to understanding how the brain, including the human brain, encodes memories in ways that lead to their stabilization or alternatively, to their erasure.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Method to Extend Research in Time (MERIT) Award (R37)
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Neurobiology of Learning and Memory Study Section (LAM)
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Morris, Jill A
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Scripps Florida
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
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:
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Cervantes-Sandoval, Isaac; Chakraborty, Molee; MacMullen, Courtney et al. (2016) Scribble Scaffolds a Signalosome for Active Forgetting. Neuron 90:1230-1242
Gai, Yunchao; Liu, Ze; Cervantes-Sandoval, Isaac et al. (2016) Drosophila SLC22A Transporter Is a Memory Suppressor Gene that Influences Cholinergic Neurotransmission to the Mushroom Bodies. Neuron 90:581-95
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

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