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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37NS019904-31
Application #
8626252
Study Section
Neurobiology of Learning and Memory Study Section (LAM)
Program Officer
Morris, Jill A
Project Start
1987-12-01
Project End
2016-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
31
Fiscal Year
2014
Total Cost
$425,250
Indirect Cost
$200,250
Name
Scripps Florida
Department
Type
DUNS #
148230662
City
Jupiter
State
FL
Country
United States
Zip Code
33458
Drago, Ilaria; Davis, Ronald L (2016) Inhibiting the Mitochondrial Calcium Uniporter during Development Impairs Memory in Adult Drosophila. Cell Rep 16:2763-76
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 14:1698-709
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
Busto, Germain U; Guven-Ozkan, Tugba; Chakraborty, Molee et al. (2016) Developmental inhibition of miR-iab8-3p disrupts mushroom body neuron structure and adult learning ability. Dev Biol 419:237-249
Cervantes-Sandoval, Isaac; Chakraborty, Molee; MacMullen, Courtney et al. (2016) Scribble Scaffolds a Signalosome for Active Forgetting. Neuron 90:1230-42
Tonoki, Ayako; Davis, Ronald L (2015) Aging impairs protein-synthesis-dependent long-term memory in Drosophila. J Neurosci 35:1173-80
Busto, Germain U; Guven-Ozkan, Tugba; Fulga, Tudor A et al. (2015) microRNAs That Promote or Inhibit Memory Formation in Drosophila melanogaster. Genetics 200:569-80
Walkinshaw, Erica; Gai, Yunchao; Farkas, Caitlin et al. (2015) Identification of genes that promote or inhibit olfactory memory formation in Drosophila. Genetics 199:1173-82
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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