Muscarinic regulation of plasticity in the brain

毒蕈碱对大脑可塑性的调节

• 批准号: 7192420
• 负责人: GENE E ROBINSON
• 金额: $ 26.59万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7192420
• 关键词: Aging; Animals; Apis; Bees; Behavior; Behavioral; Biogenic Amines; Biological Assay; Biological Models; Brain; Brain Injuries; Candidate Disease Gene; Cells; Cholinergic Agents; Cholinergic Receptors; Condition; Coupled; Coupling; Dendrites; Development; Drosophila genus; Foundations; Future; Gene Expression; Genes; Genetic; Genome; Goals; Gold; Golgi Apparatus; Growth; Honey; Hormones; Human; In Situ Hybridization; Individual; Insecta; Investigation; Knowledge; Laboratories; Learning; Length; Letters; Link; Lobe; Longevity; Mediating; Memory; Methods; Microarray Analysis; Modeling; Molecular; Molecular Biology; Muscarinic Acetylcholine Receptor; Muscarinic Agonists; Muscarinic Antagonists; Muscarinics; Mushroom Bodies; Nervous System Physiology; Nervous system structure; Neuroanatomy; Neuronal Plasticity; Neurons; Neuropil; Nicotinic Agonists; Numbers; Pathway interactions; Pattern; Performance; Pharmacology; Phenotype; Pilocarpine; Pollen; Polymerase Chain Reaction; Process; Psyche structure; Public Health; Regulation; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Sensory; Signal Transduction; Solid; Structure; Techniques; Testing; Translating; Urticaria; Week; Work; base; body volume; brain volume; cholinergic; design; experience; genome sequencing; improved; insight; mature animal; neurotransmission; neurotransmitter agonist; novel; postsynaptic; programs; psychobiology; research study; therapy development; tool

DESCRIPTION (provided by applicant): This project is designed to elucidate mechanisms that translate experience into changes in brain structure that allow adult animals to enhance their behavioral performance. Our model system, foraging-induced growth of the mushoom bodies (insect brain center for learning and memory) in the honey bee, permits investigations at the behavioral, cellular, and molecular levels. Our proposal is based on the surprising, but robust, demonstration that treatment of caged bees with a muscarinic agonist, pilocarpine, results in brain plasticity identical to that produced by a week of real foraging experience. We will: 1. determine how signaling via cholinergic pathways is related to foraging-induced increases in the volume of mushroom body neuropil using a novel experience-replacement technique; 2. determine the cellular phenotype of pilocarpine-induced changes in mushroom body neurons (Kenyon cells) using the Golgi technique; and 3. identify genes expressed in the mushroom bodies responsive to signaling via muscarinic pathways using whole bee genome microarrays, and then confirm and extend these results with quantitative RT-PCR and in situ hybridization. The bee provides a superb model system for these studies because appropriate tools, such as a sequenced genome, are now available, and because it is possible to rigorously manipulate the experience of the bee under naturalistic conditions and study effects at the neuroanatomical and molecular levels. The principal significance of this research is that it will reveal how experience is coupled to brain plasticity. Extensive conservation of nervous system function at the molecular level across the animal kingdom makes the results of our investigations on an insect broadly applicable within the field of behavioral development. This research is relevant to public health because experiments that can be efficiently performed using the simpler insect nervous system are likely to reveal how learning changes the brain in all animals, including humans. Such understanding is the first step in the development of therapies to improve human learning after brain damage. Our results will also suggest directions for the development of treatments for the decline in mental function that accompanies human aging.

描述（由申请人提供）：该项目旨在阐明将经验转化为大脑结构变化的机制，使成年动物能够增强其行为表现。我们的模型系统，觅食诱导的mushoom机构（昆虫大脑的学习和记忆中心）在蜜蜂的增长，允许在行为，细胞和分子水平的调查。我们的建议是基于令人惊讶的，但强大的，证明用毒蕈碱激动剂毛果芸香碱治疗笼中蜜蜂，结果大脑可塑性与一周的真实的觅食经验相同。我们将：1.使用一种新的经验替代技术，确定通过胆碱能通路的信号传导如何与觅食诱导的蘑菇体神经元体积增加相关; 2.使用高尔基体技术确定毛果芸香碱诱导的蘑菇体神经元（Kenyon细胞）变化的细胞表型;以及3.使用全蜂基因组微阵列鉴定蘑菇体中响应于通过毒蕈碱途径的信号传导的基因，然后用定量RT-PCR和原位杂交确认和扩展这些结果。蜜蜂为这些研究提供了极好的模型系统，因为现在已经有了适当的工具，例如测序的基因组，并且可以在自然条件下严格操纵蜜蜂的经验并研究神经解剖学和分子水平的影响。这项研究的主要意义在于它将揭示经验如何与大脑可塑性相结合。神经系统功能在动物界分子水平上的广泛保护，使得我们对昆虫的研究结果在行为发育领域具有广泛的适用性。这项研究与公共卫生有关，因为可以使用更简单的昆虫神经系统有效地进行的实验可能会揭示学习如何改变包括人类在内的所有动物的大脑。这样的理解是开发治疗方法以改善脑损伤后人类学习的第一步。我们的研究结果也将为伴随人类衰老的精神功能下降的治疗方法的发展提供方向。