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
Chihara, Takahiro; Kitabayashi, Aki; Morimoto, Michie et al. (2014) Caspase inhibition in select olfactory neurons restores innate attraction behavior in aged Drosophila. PLoS Genet 10:e1004437
Guven-Ozkan, Tugba; Davis, Ronald L (2014) Functional neuroanatomy of Drosophila olfactory memory formation. Learn Mem 21:519-26
Tan, Ying; Yu, Dinghui; Busto, Germain U et al. (2013) Wnt signaling is required for long-term memory formation. Cell Rep 4:1082-9
Cervantes-Sandoval, Isaac; Martin-Pena, Alfonso; Berry, Jacob A et al. (2013) System-like consolidation of olfactory memories in Drosophila. J Neurosci 33:9846-54