Aminergic regulation and neuroanatomy of social status in Drosophila

果蝇社会地位的胺能调节和神经解剖学

基本信息

批准号：
9096835
负责人：
Ysabel Milton Giraldo
金额：
$ 5.61万
依托单位：
CALIFORNIA INSTITUTE OF TECHNOLOGY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-07-01 至 2017-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9096835
关键词：
Address Affect Aggressive behavior Animal Model Animals Automobile Driving Behavior Behavioral Assay Biogenic Amines Biological Models Brain region Complex Cycloheximide Dementia Dominant-Negative Mutation Dopamine Drosophila genus Drosophila melanogaster Enhancers Environment Female Food Food Access Genetic Genetic Models Goals Health Horns Hour Human Individual Insecta Invertebrates Lateral Learning Libraries Memory Memory impairment Methods Modeling Molecular Molecular Genetics Mushroom Bodies Neuroanatomy Neurons Neurotransmitters Octopamine Organism Partner in relationship Pattern Pharmacological Treatment Pharmacology Phase Population Process Protein Biosynthesis Proteins Protocols documentation Regulation Research Role Serotonin Social Dominance Social Environment Social Interaction Social status Synapses Synaptic Potentials System Techniques Temperature Testing Training Vertebrates Work base behavior test combinatorial conditioning cytotoxic developmental disease environmental change fight against fighting fly food resource genetic approach insight long term memory male memory consolidation neurochemistry neuronal circuitry neurotransmission novel reconstruction relating to nervous system sex social social learning social model tool

项目摘要

DESCRIPTION (provided by applicant): Learning and memory are fundamental components of how animals and humans navigate their world and adjust to environmental changes. These changes can include social interactions, which have particular importance for social animals, including humans. However, the neural basis of social learning is poorly understood. In order to uncover the specific neurochemicals and even individual neurons responsible for this memory, a tractable model system is necessary. The fruit fly, Drosophila melanogaster, is a premier genetic model organism with a large molecular genetic toolkit and has proven successful in establishing the molecules, brain regions, and in some cases individual neurons, responsible for conditioned memory. Indeed serotonin, dopamine, and octopamine have all be associated with various types of learning and memory. In anatomical studies, brain regions including the mushroom bodies, central complex, and lateral horn are important for learning and memory. The approach taken in this proposal is to apply these techniques to fruit fly fighting and the establishment of dominance relationships, which can serve as a social model of learning. Males fight over food and mates often forming dominance relationships. Following even a single fight, losers are likely to lose subsequent fights and fight at lower intensity against familiar than unfamiliar opponents, thus developing a "loser mentality." Previous work has shown that the loser mentality persists for at least 24 hours, but the duration of this memory and whether it has a protein synthesis requirement remain unknown. Furthermore, the neurons responsible for consolidation of this memory have not been identified. This system represents an ideal one to test whether serotonin or small groups of serotonergic neurons are responsible for memory consolidation in the loser mentality. Further studies will address whether dopaminergic or octopaminergic neurons affect learning and memory. To accomplish these goals three specific aims are proposed: (1) to characterize the type of memory involved in the formation of the loser mentality using behavioral tests, pharmacology, and genetic drivers; (2) to test whether serotonin modulation affects memory consolidation using a combinatorial genetic approach; and (3) to identify and manipulate restricted populations of serotonergic or other aminergic neurons that modulate memory consolidation using intersectional genetics. If specific neurons are identified that are responsible for memory consolidation, potential synaptic connectivity can begin to be identified using a split gfp (GRASP, GFP Reconstruction Across Synaptic Partners). The proposed research has the potential to identify the specific neurons and neurochemicals responsible for the consolidation of memory in a loser mentality. Furthermore, this work will advance fruit fly aggression as a novel model for understanding socially-induced learning and identifying the neural basis of behavior.

描述（由申请人提供）：学习和记忆是动物和人类如何驾驭世界和适应环境变化的基本组成部分。这些变化可能包括社会互动，这对于包括人类在内的社会动物特别重要。然而，人们对社会学习的神经基础知之甚少。为了揭示负责这种记忆的特定神经化学物质甚至单个神经元，需要一个易于处理的模型系统。果蝇（Drosophila melanogaster）是一种重要的遗传模型生物，具有大型分子遗传工具包，并已被证明可以成功地建立负责条件记忆的分子、大脑区域，以及在某些情况下的单个神经元。事实上，血清素、多巴胺和章鱼胺都与各种类型的学习和记忆有关。在解剖学研究中，包括蘑菇体、中央复合体和侧角在内的大脑区域对于学习和记忆非常重要。该提案采取的方法是将这些技术应用于果蝇战斗和优势关系的建立，这可以作为学习的社会模型。雄性会为了食物而打架，配偶之间常常会形成支配关系。即使是一场战斗之后，失败者也可能会输掉接下来的战斗，并且与熟悉的对手相比，战斗强度会比不熟悉的对手低，从而形成“失败者心态”。此前的研究表明，失败者心态会持续至少24小时，但这种记忆的持续时间以及是否具有蛋白质合成需求仍然未知。此外，负责巩固这种记忆的神经元尚未被识别。该系统是测试血清素或一小群血清素能神经元是否负责失败者心态中的记忆巩固的理想系统。进一步的研究将解决多巴胺能或八巴胺能神经元是否影响学习和记忆。为了实现这些目标，提出了三个具体目标：（1）利用行为测试、药理学和遗传驱动因素来表征失败者心态形成中涉及的记忆类型； (2) 使用组合遗传方法测试血清素调节是否影响记忆巩固；（3）利用交叉遗传学来识别和操纵限制性的血清素能或其他胺能神经元群体，这些神经元能够调节记忆巩固。如果识别出负责记忆巩固的特定神经元，则可以使用 split gfp（GRASP，跨突触伙伴的 GFP 重建）开始识别潜在的突触连接。拟议的研究有可能识别出负责巩固失败者心态中的记忆的特定神经元和神经化学物质。此外，这项工作将推动果蝇攻击性成为理解社会诱导学习和识别行为神经基础的新模型。