GENETIC DISSECTION OF NEUROMODULATORY FUNCTIONS

描述：(改编自申请人的摘要) 神经调节对行为可塑性很重要。总目标 这项研究的目的是探索这一分子和生化性质 链接。果蝇新的多巴胺和章鱼胺受体已被发现 分离并显示在蘑菇中有高度丰富的表达 身体是嗅觉学习不可或缺的大脑结构。这个 受体产生cAMP和细胞内钙离子增加，关键 突触关键的信号转导通路的介体 可塑性。利用最近分离的受体突变体，研究将 重点解决三个根本性问题。1)受体是否 在联想学习中发挥作用？2)受体突变体在 所有类型的学习还是有选择性缺陷？3)哪种效应器 系统，cAMP和/或钙离子，对任何行为缺陷负责 观察？鉴于行为的多样性和复杂性，比较 对行为范式中受体突变的研究应该会有所帮助 剖析行为背后复杂的生理过程 可塑性。这些研究可能有助于理解生物起源的作用 人类疾病中的胺，如精神分裂症，以及 认知中的生物胺受体。

DESCRIPTION: (Adapted From The Applicant's Abstract) Neuromodulation is important for behavioral plasticity. The overall goal of this study is to explore the molecular and biochemical nature of this link. Novel dopamine and octopamine receptors of Drosophila have been isolated and shown to have highly enriched expression in the mushroom bodies, a brain structure indispensable for olfactory learning. The receptors produce increases in cAMP and intracellular Ca2+, key mediators of signal transduction pathways crucial for synaptic plasticity. Using recently isolated receptor mutants, the studies will focus on addressing three fundamental questions. 1) Do the receptors play a role in associative learning? 2) Do the receptor mutants fail at all types of learning or is there a selective deficit? 3) Which effector systems, cAMP and/or Ca2+, are responsible for any behavioral deficits observed? Given the diversity and complexity of behavior, comparative studies of the receptor mutants in behavioral paradigms should help dissect the elaborate physiological processes underlying behavioral plasticity. These studies may help to understand the roles for biogenic amines in human diseases, such as schizophrenia, and the actions of biogenic amine receptors in cognition.