Simultaneous in vivo studies of synapses, neurons, and learning and memory

描述 摘要： 学习和记忆的能力对生活的各个方面都是必不可少的。为了更好地理解这些过程与健康和疾病的关系，我们提出了一种新的方法来研究神经回路如何计算，存储信息和控制行为。我们将开发新的策略和技术，用于同时测量活体动物的学习行为、突触可塑性和神经元活动。我们预测，简单生物体中的微电路将更容易处理这些研究，并且所学到的经验教训将与包含更多和更复杂电路的复杂神经系统直接相关。因此，我们计划将我们的研究计划集中在线虫C的简单神经系统中识别的微电路上。elegans和解决以下问题：a）突触可塑性发生了什么变化，这些变化是如何控制的？B）突触可塑性如何导致神经元和网络活动的长期变化？c）神经网络如何计算信息和控制行为？为了开始解决上述问题，我们需要新的工具和技术来帮助我们实现测量学习过程中发生的突触变化的目标。为此，我们将开发基于微流体的条件学习范例;用于增强突触蛋白检测的镧系元素发光技术;以及使用电压敏感染料进行神经元活性体内测量的新策略。这些新技术的发展将允许实时测量学习过程中发生的变化，并更好地了解有助于学习和记忆的分子机制。为了补充这种方法，我们还将开发用于识别和快速克隆这些复杂过程所需的新基因的遗传策略。 公共卫生相关性： 学习和记忆的能力对于幸福和富有成效的生活至关重要。即使是轻微的脱发

DESCRIPTION Abstract: The ability to learn and remember is essential for all aspects of life. To better understand these processes in relation to health and disease, we propose a new approach to studying how neural circuits compute, store information and control behavior. We will develop new strategies and techniques for simultaneous measurements of learned behaviors, synaptic plasticity, and neuronal activity in a live animal. We predict that microcircuits in simple organisms will be more tractable to these studies and that the lessons learned will be of immediate relevance to complex nervous systems that contain more numerous and elaborate circuits. Therefore, we plan to focus our research program on identified microcircuits in the simple nervous system of the nematode C. elegans and address the following questions: a) What changes occur during synaptic plasticity and how are these changes controlled? b) How does synaptic plasticity lead to long-lived changes in neuronal and network activity? c) How do neural networks compute information and control behavior? To begin to address the above questions, we need new tools and techniques that will facilitate our goal to measure synaptic changes that occur during learning. Towards this end, we will develop microfluidics-based conditional learning paradigms; lanthanide-based luminescence techniques for enhanced detection of synaptic proteins; and new strategies for in vivo measurements of neuronal activity using voltage-sensitive dyes. The development of these new techniques will allow real-time measurements of the changes that occur during learning and offer a better understanding of the molecular mechanisms that contribute to learning and memory. To compliment this approach, we will also develop genetic strategies for the identification and rapid cloning of new genes required for these complex processes. Public Health Relevance: The ability to learn and remember is essential for a happy and productive life. Even mild loss of one's mem