Activity-dependent Synaptic and Circuit Plasticity

 描述(申请人提供)：大脑通过在突触传递信号来处理信息和产生行为，突触将神经元连接到巨大的通信细胞网络。这些被称为神经回路的网络不是一成不变的，而是在一生中随着经验的变化而改变的。这种神经回路的可塑性对于大脑的正常发育和执行包括学习和记忆在内的所有重要功能至关重要。然而，当大脑可塑性机制功能异常时，毁灭性的精神疾病往往随之而来。因此，神经科学研究的一个主要目标是了解经验产生的大脑活动改变神经回路行为的详细机制。这在很大程度上是因为神经活动不断地调整神经元之间突触交流的效率或强度，这一过程被称为突触可塑性。尽管突触可塑性对大脑发育和更高的大脑功能非常重要，但除了通常由细胞内钙水平的活动依赖性变化引发的分子机制外，人们对突触可塑性的了解相对较少。这个Conte中心将汇集四位领先的研究人员，继续他们之前的努力，使用创新的分子遗传操作，结合复杂和独特的生化、电生理和成像分析，阐明不同形式突触可塑性背后的高度新颖的机制，以及这些形式的突触可塑性如何在适应性和病理形式的经验依赖性可塑性中发挥作用，包括学习和记忆。这个孔特中心对突触和电路可塑性机制的新见解将影响到广泛从事与正常和病理大脑功能相关的主题的神经科学家。该中心还将为研究界提供新的分子遗传学工具和转基因小鼠，可用于操纵对整个大脑突触可塑性至关重要的蛋白质，以探索这些关键蛋白质在参与广泛正常和病理行为的特定细胞类型中的作用。因此，该中心将为神经科学研究中最重要的领域之一提供技术和智力创新，对我们理解正常和疾病的大脑功能具有广泛的影响。神经细胞之间交流的有效性是由经验改变的，这些改变对包括学习和记忆在内的所有正常大脑功能至关重要。该中心的目标是确定导致这些修饰的分子机制。这些信息将有助于更好地了解精神疾病的原因，并最终开发出更有效的治疗方法。

 DESCRIPTION (provided by applicant): The brain processes information and generates behavior by transmitting signals at its synapses, which connect neurons into vast networks of communicating cells. These networks, known as neural circuits, are not static but are modified throughout life by experience. Such neural circuit plasticity is critical for the brain to develop normally and perform all of its important functions, including learning and memory. When brain plasticity mechanisms function abnormally, however, devastating mental illnesses often ensue. Thus, a major goal of neuroscience research is to understand the detailed mechanisms by which the brain activity generated by experiences modifies neural circuit behavior. This occurs in large part because neural activity continually adjusts the efficiency or strength of synaptic communication between neurons, a process known as synaptic plasticity. Despite the importance of synaptic plasticity for brain development and higher brain functions, relatively litte is known about its molecular mechanisms other than it is commonly triggered by activity- dependent changes in intracellular calcium levels. This Conte Center will bring together four leading investigators to continue their previous efforts to use innovative molecular genetic manipulations combined with sophisticated and unique biochemical, electrophysiological, and imaging assays to elucidate highly novel mechanisms that underlie different forms of synaptic plasticity and how these forms of synaptic plasticity play a role in adaptive and pathological forms of experience-dependent plasticity, including learning and memory. The new insights into synaptic and circuit plasticity mechanisms generated by this Conte Center will influence a broad array of neuroscientists working on a wide range of topics related to normal and pathological brain function. The Center will also provide the research community with novel molecular genetic tools and genetically modified mice that can be used to manipulate proteins critical for synaptic plasticity throughout the brain to explore the roles of these critical proteins in specifi cell types that participate in a wide range of normal and pathological behaviors. Thus the Center will provide both technological and intellectual innovations to one of the most important areas of neuroscience research with far ranging implications for our understanding of normal and diseased brain function. Relevance The effectiveness of communication between nerve cells is modified by experience and these modifications are crucial for all normal brain functions including learning and memory. The goal of this Center is to determine the molecular mechanisms that are responsible for these modifications. Such information will lead to a better understanding of the causes of mental illness and eventually to the development of more efficacious treatments