Functional characterization of an insulin-like peptide network that regulates lea

调节 lea 的类胰岛素肽网络的功能表征

• 批准号: 8614331
• 负责人: Yun Zhang
• 金额: $ 56.26万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-05 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8614331
• 关键词: Address; Animals; Architecture; Behavior; Behavior Disorders; Behavioral; Behavioral Assay; Biological Assay; Budgets; Caenorhabditis elegans; Calcium; Cells; Cognitive; Congenital Abnormality; Cues; Defect; Development; Disease; Environment; Funding; Genes; Genetic; Genome; Genotype; Grant; Human; Human Development; Image; Insulin; Learning; Link; Longevity; Malignant Neoplasms; Maps; Measures; Memory; Metabolic syndrome; Metabolism; Molecular; Mutation; Neurons; Neurophysiology - biologic function; Olfactory Learning; Output; Pathology; Pathway interactions; Pattern; Peptide Signal Sequences; Peptides; Phenotype; Physiological; Play; Process; Property; Regulation; Role; Signal Pathway; Signal Transduction; Site; System; Testing; Tissues; base; cellular targeting; combinatorial; human disease; in vivo; insight; learned behavior; learning ability; loss of function; member; mutant; neural circuit; overexpression; relating to nervous system; response

To survive, animals have to optimize their physiological and behavioral responses based on specific environmental cues. Through conserved signaling mechanisms, the insulin/insulin-like peptide (ILP) pathway plays essential roles in this process by regulating development, metabolism and life span in response to internal and external environments. Intriguingly, ILP signaling also regulates learning and memory, suggesting that ILPs act as a link between environment and neural function to generate optimal behavioral outputs. However, the molecular and cellular mechanisms through which ILPs regulate learning remain largely uncharacterized. Many animals, including humans, encode multiple ILPs in their genomes, such as the 40 ILPs in C. elegans, suggesting functional diversity and potential interaction among them. Recently, two C. elegans ILPs, INS-6 and INS-7, are shown to play opposite roles in regulating aversive olfactory learning. The observation that INS-6 inhibits ins-7 in this process and that the expression of these two ILPs are regulated by other ILPs suggest the existence of an ILP network that modulates behavior. Because INS-6 and INS-7 appear to coordinate the animal's behavioral responses with its physiological state, this further suggests that this network's regulation of learning involves environmental context. This R01 will test this hypothesis through the following: (1) define the ILP network composition and architecture that regulates learning; (2) map the cellular circuitry through which this network functions; and (3) demonstrate how environment modulates the activity of the ILP learning network. To address these aims, this R01 will involve high-throughput learning behavioral assays and in vivo calcium imaging of neuronal activities in different ILP mutant backgrounds and under different conditions. Finally, completion of this R01 will illustrate how the ILP network optimizes learning behavior to increase survival under different environments.

为了生存，动物必须根据特定的环境优化其生理和行为反应。 环境线索通过保守的信号传导机制，胰岛素/胰岛素样肽（ILP）途径 在这一过程中起着至关重要的作用，通过调节发育、代谢和寿命， 内部和外部环境。有趣的是，ILP信号也调节学习和记忆，这表明 ILP作为环境和神经功能之间的联系，以产生最佳的行为输出。 然而，ILP调节学习的分子和细胞机制仍然主要是 没有特征的包括人类在内的许多动物在其基因组中编码多个ILP，例如40个ILP。 in C. elegans，表明功能多样性和潜在的相互作用。最近，两个C。elegans INS-6和INS-7在调节厌恶性嗅觉学习中起相反的作用。的 观察到INS-6在此过程中抑制INS-7，并且这两种ILP的表达受 其它ILP暗示存在调节行为的ILP网络。因为INS-6和INS-7出现了 协调动物的行为反应与其生理状态，这进一步表明， 网络对学习的调节涉及到环境语境。本R 01将通过 以下内容：（1）定义调节学习的ILP网络组成和架构;（2）绘制细胞 该网络的功能;（3）演示环境如何调节 ILP学习网络为了实现这些目标，R 01将涉及高通量学习行为 在不同ILP突变体背景下和在不同ILP突变体背景下， 不同条件最后，完成本R 01将说明ILP网络如何优化学习 提高在不同环境下的生存能力。