The goal of this research project is to define the logic by which the brain organizes different types of memories among its component neurons. The project contrasts how the brain organizes olfactory memories learned in association with a rewarding cue and those learned in association with an aversive cue, and delves into some of the underlying mechanisms. The research project utilizes the model system Drosophila melanogaster because of the ease in conditioning the fly using olfactory cues and because of the ability to peer into the brain of living animals and watch the activity of different sets of neurons. The latter approach, functional optical cellular imaging, employs flies carrying transgenes expressing 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. To date, six different cellular memory traces have been defined using aversive olfactory conditioning. These traces form in different sets of neurons in the olfactory nervous system and occur with differing temporal dynamics. The memory traces that occur within these same neurons after a rewarding olfactory conditioning event will be examined along with the molecular mechanisms underlying memory trace formation. Since nearly every neuropsychiatric disorder affects memory formation, these studies will aid in understanding memory formation in the normal brain as well as in the diseased brain.

Public Health Relevance

The majority of human neurological and psychiatric disorders involve impairment in learning and memory. This project will examine the logic of how the brain encodes different types of memories, contrasting memories associated with rewarding cues versus memories associated with aversive cues, along with detailing the underlying molecular mechanisms. We will utilize the model Drosophila melanogaster - because of the ease of studying memory formation in this organism and the ability to peer into its brain and watch the activity of neurons during learning - to obtain knowledge that will contribute to understanding how the brain, including the human brain, organizes different types of memories and how brain disorders disrupt learning and memory.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Research Project (R01)
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Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Mamounas, Laura
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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
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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