Octopamine Neuroanatomy and Functioning in Fruit Fly Social Behavior

描述（由申请人提供）：攻击性是一种天生的行为特征，具有多种生态功能。在理解攻击的神经生物学的基础研究已经使用无脊椎动物和脊椎动物模型系统进行。尽管进行了广泛的研究，但对于特定的分子/细胞因素如何组织发育中的神经系统来规划攻击行为，人们知之甚少。果蝇（Drosophila melanogaster）基因组被完全测序，作为一个模型系统，果蝇为行为和基因操作提供了许多可能性，包括复杂的成像技术。该提案将使用果蝇作为模型系统来研究大脑的神经化学遗传组织及其与编程社会行为的相关性。果蝇的攻击性和求偶行为是两性二态的——雄性向雌性求爱，并使用与雌性不同的战斗行为模式。这些行为上的性别差异是由性别决定等级中的基因直接控制的，包括无果性（fru）。无果基因表现出性别特异性的选择性剪接。雌性会产生一个截断的信息，不产生蛋白质。如果雌性产生雄性剪接的变体，它们就会表现出雄性的求爱和攻击行为。没有雄性剪接变异的雄性不会向雌性求爱，表现出雌性的战斗模式，并且是不育的。直到最近，显示fru共表达的特定神经激素/神经递质系统尚不清楚。有趣的是，去甲肾上腺素的苯酚类似物-章鱼胺（OA），通常存在于无脊椎动物物种中，最近被发现在雄性果蝇的求爱或战斗决策中起着关键作用。在果蝇的大脑中发现了大约100个OA神经元。这些OA神经元中只有三个共同表达雄性形式的fru （FruM）。先前的研究结果表明，这些FruM/OA细胞参与了雄性在求爱和攻击之间的决策。然而，与这些FruM/OA神经元相关的电路及其在协调感觉输入和运动输出以驱动果蝇社会行为中的特定生理作用尚不清楚。通过使用组合遗传方法，该提案的结果应该：首先，允许构建行间交叉数据库，从而允许直接操纵单个或小群OA神经元中的基因；然后，提供一个模型来检验敲除、增强或降低这些神经元功能的行为后果。这一研究项目代表了阐明果蝇社会行为背后的神经回路的第一步。

DESCRIPTION (provided by applicant): Aggression is an innate behavioral trait that has numerous ecological functions. Basic research in understanding the neurobiology of aggression has been performed using both invertebrate and vertebrate model systems. Despite extensive study, relatively little is known regarding how specific molecular/cellular factors organize the developing nervous system to program aggressive behavior. The fruit fly (Drosophila melanogaster) genome is fully sequenced, and as a model system, fruit flies offer numerous possibilities for behavioral and genetic manipulation, including sophisticated imaging techniques. This proposal will use Drosophila as a model system to study the neurochemical genetic organization of the brain and its relevance to programming social behavior. The display of aggression and courtship behavior in the fruit fly is sexually dimorphic - with males courting females and using different patterns of fighting behavior than females. These behavioral sex differences are under the direct control of genes of the sex determination hierarchy, including fruitless (fru). The fruitless gene displays sex- specific alternative splicing. Females make a truncated message that makes no protein. If females make the male-spliced variant, they display male-like courtship and aggressive behaviors. Males that do not make the male-spliced variants do not court females, display female patterns of fighting, and are infertile. Until recently, the specific neurohormonal/neurotransmitter systems that show co-expression of fru were unknown. Interestingly, the phenol analogue of norepinephrine - octopamine (OA), which is commonly found in invertebrate species, was recently found to play a critical role in decisions made by male flies to either court or fight. Approximately 100 OA neurons are found in the fly brain. Only three of these OA neurons co-express the male forms of fru (FruM). The results from previous work have demonstrated that these FruM/OA cells are involved in decision making by males between courtship and aggression. However, the circuitry involved with these FruM/OA neurons and their specific physiological roles in coordinating sensory input and motor output to drive social behavior in flies is unclear. By utilizing a combinatorial genetic approach, the results from this proposal should: first, allow the construction of a database of crosses between lines that will allow for direct manipulation of genes in individual or small groups of OA neurons; and then, provide a model to examine the behavioral consequences of knocking out, enhancing or reducing the function of these neurons. This research program represents first steps in elaborating the neural circuitry underlying social behavior in fruit flies. PUBLIC HEALTH RELEVANCE: Because of their genetic pliability, fruit flies (Drosophila melanogaster) are a superior model system to evaluate the neurogenetics of behavior. Approximately 75% of genes encoding human diseases have a fly equivalent, allowing scientists to translate basic neurogenetic information from flies to humans. Results from this proposal have the potential to reveal novel gene families and transcription factors programming the neural circuitry underlying the establishment and maintenance of patterns of social behavior in organisms, up to and including humans.