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方方面面都是必不可少的。为了更好地理解这些与健康和疾病有关的过程，我们提出了一种新的方法来研究神经电路如何计算、存储信息和控制行为。我们将开发新的策略和技术来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进行这些研究，所学到的经验将直接适用于包含更多和更复杂的电路的复杂神经系统。因此，我们计划将研究重点放在线虫简单神经系统中识别的微电路上，并解决以下问题：a)在突触可塑性过程中发生了什么变化，以及这些变化是如何控制的？B)突触的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促进我们的目标，以测量在学习过程中发生的突触变化。为此，我们将开发基于微流体的条件学习范例；基于镧系元素的发光技术，以增强突触蛋白的检测；以及使用电压敏感染料在体内测量神经元活动的新策略。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，并提供对有助于学习和记忆的分子机制的更好理解。为了补充这一方法，我们还将开发识别和快速克隆这些复杂过程所需的新基因的遗传策略。

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.