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Epigenetic Reprogramming of Behaviors with Sensory Experience

通过感官体验对行为进行表观遗传重编程

基本信息

批准号：
10159324
负责人：
Corbin D Jones
金额：
$ 38.55万
依托单位：
DUKE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-05-15 至 2023-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10159324
关键词：
Adult Afferent Neurons Anatomy Animal Model Anxiety Behavior Behavioral Binding Calcium Calcium Signaling Chemicals Chromatin Co-Immunoprecipitations Cognition Disorders Complex Courtship Cues DNA Methylation Disease Drosophila genus EP300 gene Environment Epigenetic Process Food Future Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Genetic Transcription Goals Histones Hormone Receptor Housing Human Immunoprecipitation Juvenile Hormones Lead Ligands Link Maintenance Mediating Modeling Modification Molecular Nervous system structure Neurons Odorant Receptors Odors Olfactory Receptor Neurons Pheromone Physiology Property Publishing Receptor Signaling Reporting Role Sensory System Testing Therapeutic Transferase Work autism spectrum disorder base chromatin immunoprecipitation chromatin modification epigenetic regulation experience experimental study fly hormonal signals male mating behavior men&apos s group mutant neural circuit neurophysiology neuropsychiatric disorder novel therapeutic intervention olfactory receptor palmitoleic acid programs promoter relating to nervous system response sex social social deficits transcription factor

项目摘要

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. .

基因表达的表观遗传调控与长期的行为行为有关