Epigenetic regulation of gene expression is associated with long-lasting behavioral changes in animal models and humans. In response to environmental cues, epigenetic programs regulate gene expression in matured neurons via chromatin modifications and DNA methylation resulting in enduring neurophysiological changes. There is mounting evidence to implicate the involvement of dysfunctional epigenetic programs in many cognitive and neuropsychiatric disorders. However, establishing a causal link between epigenetic mechanism and neuronal properties that underlie behavioral adaptation in complex nervous systems has been difficult, mainly due to the paucity of behaviorally relevant neural and genetic substrates that are targeted by epigenetic regulation. Our goal is to determine the epigenetic basis of sensory experience-dependent changes in neurophysiology and behavior. We take advantage of the anatomical simplicity and the powerful genetic toolkit of the Drosophila olfactory receptor neurons (ORNs) involved in courtship behaviors, and the well- established Drosophila male courtship behavior, a robust ritualistic behavior governed by a single gene, fruitlessM (fruM) expressed in approximately 2000 interconnected neurons. Our pilot experiments and recent studies show that olfactory experience enhances the response of the Or47b and Ir84a ORNs in males and male courtship behavior. We also have linked olfactory receptor (OR) signaling through calcium, and histone acetyl transferase p300 to the expression of the transcriptional factor fruM as a molecular mechanism by which olfactory experience regulates neurophysiology and behavior. We hypothesize that fly and food odors in the environment lead to chromatin dependent changes in fruM transcription in sensory neurons to modify neurophysiology and courtship behavior with olfactory experience. To test this, we will first determine the effect of chromatin modulation by p300 on reprogramming neurophysiology and behavior. Next, we will characterize the molecular mechanisms by which olfactory experience and chromatin modulates fruM expression. Finally, we will determine the transcriptional and chromatin changes in ORNs with olfactory experience. .

Public Health Relevance

Our work will reveal common mechanisms of epigenetic modulation of gene expression and behavior with sensory experience. Thus, in the future, our findings can lead to creative sensory experience-based therapeutic strategies that harness similar types of plasticity against neuropsychiatric disorders, such as autism spectrum disorders, where misprocessing of sensory experience accentuates anxiety and social deficits associated with the disease.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS109401-02
Application #
9696417
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Riddle, Robert D
Project Start
2018-05-15
Project End
2023-04-30
Budget Start
2019-05-01
Budget End
2020-04-30
Support Year
2
Fiscal Year
2019
Total Cost
Indirect Cost
Name
Duke University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705