Muscarinic regulation of plasticity in the brain

毒蕈碱对大脑可塑性的调节

基本信息

批准号：
7388959
负责人：
GENE E ROBINSON
金额：
$ 26.54万
依托单位：
UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
依托单位国家：
美国
项目类别：
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/7388959
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

项目摘要

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 nvestigations 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.

该项目旨在阐明将经验转化为大脑结构变化的机制这允许成年动物增强其行为表现。我们的模型系统，觅食引起的蜂蜜蜜蜂中蘑菇体的生长（昆虫脑中的学习和记忆中心），许可在行为，细胞和分子水平上进行的vestigatigatigation。我们的建议是基于令人惊讶的，但是强有力的证明，用毒蕈碱激动剂毛果碱治疗笼蜜蜂的治疗导致大脑可塑性与一周的真实觅食经验所产生的可塑性相同。我们将：1。确定如何通过胆碱能途径传导与觅食引起的蘑菇体量增加有关使用一种新颖的体验替代技术的神经肽； 2。确定毛car虫的细胞表型使用高尔基技术诱导蘑菇体神经元（Kenyon细胞）的变化；和3。识别基因在蘑菇体中表达，使用整个蜜蜂通过毒蕈碱途径响应信号基因组微阵列，然后用定量的RT-PCR和原位确认并扩展这些结果杂交。蜜蜂为这些研究提供了出色的模型系统，因为适当的工具，例如现在可以使用测序的基因组，并且因为可以严格操纵体验在自然条件下的蜜蜂和神经解剖学和分子水平的研究效果。这这项研究的主要意义是它将揭示经验如何与大脑可塑性耦合。在整个动物界的分子水平上，广泛的神经系统功能的保护使得我们对广泛适用于行为发展领域的昆虫的调查结果。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可能会揭示学习如何改变所有动物的大脑，包括人类。这种理解是发展疗法的第一步，以改善人类学习脑损伤后。我们的结果还将暗示开发衰落治疗的方向在人类衰老伴随的心理功能中。