Aminergic regulation and neuroanatomy of social status in Drosophila

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，这对包括人类在内的社会性动物尤为重要。然而，人们对社会学习的神经基础知之甚少。为了揭示特定的神经化学物质，甚至是负责这种记忆的单个神经元，一个易于处理的模型系统是必要的。果蝇（Drosophila melanogaster）是一种主要的遗传模式生物，拥有大量的分子遗传工具包，并已被证明成功地建立了负责条件记忆的分子、大脑区域和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学习和记忆非常重要。本文提出的方法是将这些技术应用于果蝇的战斗和优势关系的建立，这可以作为一种社会学习模式。雄性为食物和配偶而战，通常形成统治关系。即使在一场战斗之后，失败者也很可能在随后的战斗中失败，并且与熟悉的对手进行较低的战斗，从而形成“失败者心态”。先前的研究表明，失败者的心态至少会持续24小时，但这种记忆的持续时间以及是否需要蛋白质合成仍然未知。此外，负责巩固这种记忆的神经元尚未被确定。这个系统代表了一个理想的测试是否血清素或小组血清素能神经元负责记忆巩固在失败者的心态。进一步的研究将探讨多巴胺能或八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与失败者心态形成有关的记忆类型；(2)采用组合遗传学方法检验血清素调节是否影响记忆巩固；(3)利用交叉遗传学识别和操纵调节记忆巩固的血清素能或其他胺能神经元的有限种群。如果确定了负责记忆巩固的特定神经元，则可以开始使用分裂gfp （GRASP，跨突触伙伴gfp重建）来识别潜在的突触连接。这项拟议的研究有可能确定在失败者心态中负责巩固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作为理解社会诱导学习和识别行为神经基础的新模型。

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.