Muscarinic regulation of plasticity in the brain

该项目旨在阐明将经验转化为大脑结构变化的机制 能够让成年动物增强它们的行为表现。我们的模型系统， 蜜蜂体内Mushoom体（昆虫大脑学习和记忆中心）的生长， 行为、细胞和分子水平的研究。我们的建议是基于令人惊讶的，但 强有力的证据表明，用毒蕈碱激动剂毛果芸香碱治疗笼中蜜蜂， 可塑性与一周真实的觅食经验所产生的一致。我们将：1.确定如何 通过胆碱能途径的信号传导与觅食诱导的蘑菇体体积增加有关 使用新的经验替代技术的神经网络; 2.确定毛果芸香碱的细胞表型- 使用高尔基体技术诱导蘑菇体神经元（Kenyon细胞）的变化;以及3.识别基因 在蘑菇体中表达，对通过毒蕈碱途径的信号传导有反应， 基因组芯片，然后用定量RT-PCR和原位杂交证实和扩展这些结果， 杂交方法蜜蜂为这些研究提供了一个极好的模型系统，因为适当的工具， 一个测序的基因组，现在可以得到，因为它可以严格地操纵经验， 在自然条件下的蜜蜂，并在神经解剖学和分子水平上的研究效果。的 这项研究的主要意义在于它将揭示经验是如何与大脑可塑性联系在一起的。 在整个动物王国中，神经系统功能在分子水平上的广泛保存使得 我们对一种昆虫的研究结果广泛适用于行为发育领域。 这项研究与公共卫生有关，因为可以有效地使用 更简单的昆虫神经系统可能揭示学习如何改变所有动物的大脑，包括 人类这样的理解是开发改善人类学习的疗法的第一步 在脑损伤后我们的研究结果也将为治疗这种下降的发展提供方向。 大脑功能的变化。

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.