Muscarinic regulation of plasticity in the brain

毒蕈碱对大脑可塑性的调节

• 批准号: 7096366
• 负责人: GENE E ROBINSON
• 金额: $ 29.75万
• 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/7096366
• 关键词: Hymenoptera; arthropod genetics; behavior test; behavioral /social science research tag; biological signal transduction; brain; brain morphology; cell morphology; eating; experience; genetic models; in situ hybridization; learning; microarray technology; muscarinic receptor; neural plasticity; neural transmission; neuroanatomy; neurogenetics; neurons; neuropil; neuroregulation; phenotype; pilocarpine; Hymenoptera; arthropod genetics; behavior test; behavioral /social science research tag; biological signal transduction; brain; brain morphology; cell morphology; eating; experience; genetic models; in situ hybridization; learning; microarray technology; muscarinic receptor; neural plasticity; neural transmission; neuroanatomy; neurogenetics; neurons; neuropil; neuroregulation; phenotype; pilocarpine

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的变化的机制，从而使成年动物能够增强其行为表现。我们的模型系统是蜂蜜蜜蜂中觅食诱导的蘑菇体的生长（昆虫脑中的学习和记忆中心），可以在行为，细胞和分子水平上进行研究。我们的提议是基于令人惊讶但强大的证明，即用毒蕈碱激动剂（Pilocarpine）对笼蜜蜂进行处理，从而导致大脑可塑性与一周的真实觅食经验所产生的相同。我们将：1。确定通过胆碱能途径的信号如何使用一种新型的经验替代技术与觅食诱导的蘑菇体神经肽量增加有关； 2。使用高尔基技术来确定毛果果诱导的蘑菇体神经元（Kenyon细胞）变化的细胞表型；和3。确定使用整个蜜蜂基因组微阵列通过毒蕈碱途径响应信号的蘑菇体中表达的基因，然后用定量的RT-PCR和原位杂交确认并扩展这些结果。蜜蜂为这些研究提供了出色的模型系统，因为现在可以使用适当的工具，例如测序的基因组，并且可以在自然主义条件下严格操纵蜜蜂的经验，并且在神经解剖学和分子水平上的研究效果。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。整个动物界的分子水平上神经系统功能的广泛保护使我们对广泛适用于行为发展领域的昆虫进行了调查的结果。这项研究与公共卫生有关，因为可以使用较简单的昆虫神经系统有效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。这种理解是开发疗法以改善脑损伤后人类学习的第一步。我们的结果还将暗示开发人类衰老伴随精神功能下降的治疗方法的方向。