Neuronal basis of courtship specificity and plasticity

描述(由申请人提供)：这项拟议项目的长期目标是了解控制复杂行为的高级大脑功能背后的基本神经机制。大脑高级功能(如学习和记忆)的中断可能是由多种原因造成的，包括脑部手术、长期酗酒、头部损伤、缺氧和各种神经退行性疾病，如阿尔茨海默病。对大脑中不同解剖结构的神经元如何相互沟通以操纵复杂行为的基本了解，对于预防和治疗许多影响大脑高级功能的疾病至关重要。最近的研究表明，负责包括学习和记忆在内的重要生物过程的分子和细胞机制在远亲物种中保存得很好。在这个项目中，果蝇雄性求偶将被用作高级大脑功能的生理模型，它由一系列高度刻板的活动组成，也显示出相当大的经验依赖性可塑性。该项目的具体目标是确定参与求爱可塑性学习/记忆过程的神经元亚群，并确定记忆形成不同阶段神经元活动的时间需求。为了实现这些目标，人们建立了一种新的分子遗传学方法。在这种方法中，利用GAL4IUAS系统在限制性神经元亚群中表达了果蝇shibire基因的一个温度敏感等位基因(SHI“)。然后，目标神经元的突触传递被完好无损的动物的轻微温度变化迅速且可逆地阻止。通过利用大量特定于有限大脑区域的可用的GAL4线，特定神经元亚群在求爱可塑性中的重要性将被确定。遗传学和形态分析的结合将被用来进一步研究神经元亚群，其功能意义被揭示。同样的方法也将识别出雄性求爱中由基因决定的、刻板印象的方面所涉及的神经元亚群。预期的结果，加上果蝇行为遗传学积累的信息，将为了解果蝇高级大脑功能的神经机制提供新的见解，并将有助于发展研究包括人类在内的高等脊椎动物复杂行为的概念框架。

DESCRIPTION (provided by applicant): The long-term goal of this proposed project is to understand fundamental neuronal mechanisms underlying higher brain functions that control complex behaviors. Disruption of higher brain functions, such as learning and memory, can occur for a number of reasons including brain surgery, chronic alcohol abuse, head injury, anoxia, and various neurodegenerative disorders such as Alzheimer's disease. A basic understanding of how anatomically distinct neurons in the brain communicate with one another to manipulate complex behavior is essential for the prevention and treatment of many disorders affecting higher brain functions. Recent studies indicate that molecules and cellular mechanisms responsible for important biological processes, including learning and memory, are well conserved among distantly related species. In this project, Drosophila male courtship, which consists of a highly stereotypical sequence of activities and also shows considerable experience-dependent plasticity, will be used as a physiological model of higher-order brain functions. Specific aims of the project are to identify the neuronal subsets involved in the learning/memory process of the courtship plasticity and to determine the temporal requirements of neuronal activity during different phases of the memory formation. To accomplish these aims, a novel molecular genetic approach has been established. In this approach a temperature-sensitive allele of the Drosophila shibire gene (shi") is expressed in restricted neuronal subsets using the GAL4IUAS system. Then, synaptic transmission of the targeted neurons is blocked rapidly and reversibly by a mild temperature-shift in intact animals. By taking advantage of the large collection of available GAL4 lines that are specific to restricted brain regions, the significance of particular neuronal subsets in the courtship plasticity will be determined. A combination of genetic and morphological analysis will be applied to further investigate the neuronal subsets whose functional significance is revealed. The neuronal subsets involved in the genetically determined, stereotypical aspects of male courtship will be also identified using the same approach. The anticipated results, together with the accumulated information of Drosophila behavioral genetics, will provide new insight into the neuronal mechanisms of higher-brain functions in flies, and will contribute to the development of conceptual frameworks for the study of complex behaviors in higher vertebrates including humans.