Neuronal basis of courtship specificity and plasticity

描述（由申请人提供）：这个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的基本神经元机制。大脑高级功能（如学习和记忆）的破坏可能由于多种原因而发生，包括脑手术、慢性酒精滥用、头部损伤、缺氧和各种神经退行性疾病（如阿尔茨海默病）。对大脑中解剖学上不同的神经元如何相互通信以操纵复杂行为的基本理解对于预防和治疗影响高级大脑功能的许多疾病至关重要。最近的研究表明，负责重要生物过程，包括学习和记忆的分子和细胞机制在远亲物种中保存良好。在这个项目中，果蝇雄性求爱，其中包括一个高度刻板的活动序列，也显示出相当大的经验依赖的可塑性，将被用作高阶脑功能的生理模型。该项目的具体目标是确定参与求爱可塑性的学习/记忆过程的神经元子集，并确定在记忆形成的不同阶段神经元活动的时间要求。为了实现这些目标，一种新的分子遗传学方法已经建立。在该方法中，使用GAL 4 IUAS系统在限制性神经元亚群中表达果蝇shibire基因（shi”）的温度敏感等位基因。然后，在完整的动物中，目标神经元的突触传递通过温和的温度变化而被快速且可逆地阻断。通过利用大量的可获得的GAL 4系的优势，这些系特异于有限的脑区域，将确定特定神经元亚群在求偶可塑性中的重要性。遗传学和形态学分析的结合将被应用于进一步研究其功能意义被揭示的神经元亚群。神经元亚群参与遗传决定，男性求爱的刻板方面也将确定使用相同的方法。预期的结果，以及果蝇行为遗传学的积累信息，将提供新的见解，在苍蝇的高级脑功能的神经机制，并将有助于发展的概念框架，研究复杂的行为在高等脊椎动物包括人类。

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.