Octopamine Neuroanatomy and Functioning in Fruit Fly Social Behavior

描述(申请人提供)：攻击性是一种与生俱来的行为特征，具有许多生态功能。利用无脊椎动物和脊椎动物模型系统进行了理解攻击性神经生物学的基础研究。尽管进行了广泛的研究，但关于特定的分子/细胞因素如何组织发育中的神经系统来编程攻击行为，人们知之甚少。果蝇(果蝇)的基因组是完全测序的，作为一个模型系统，果蝇为行为和遗传操作提供了许多可能性，包括复杂的成像技术。这项提议将以果蝇为模型系统，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。果蝇的攻击性和求爱行为的表现是性二态的--雄性向雌性求爱，并使用与雌性不同的打斗行为模式。这些行为性别差异是由性别决定等级的基因直接控制的，包括无果基因(FRU)。这种没有结果的基因表现出性别特异性的选择性剪接。雌性黑猩猩传递的信息被截断，不会产生蛋白质。如果雌性产生了雄性拼接的变体，它们就会表现出类似雄性的求爱和攻击性行为。没有产生雄性剪接变体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/神经递质系统还不清楚。有趣的是，在无脊椎动物中常见的去甲肾上腺素-章鱼胺(OA)的苯酚类似物，最近被发现在雄性苍蝇做出法庭或战斗的决定时发挥关键作用。在苍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男性形式的Fru(Frum)。以前的研究结果表明，这些FRUM/OA细胞参与了雄性在求爱和攻击之间的决策。然而，这些Frum/OA神经元所涉及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方面的具体生理作用尚不清楚。通过利用组合遗传学方法，这一提议的结果应该是：首先，允许构建一个品系之间的杂交数据库，这将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。这项研究计划代表了详细阐述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.