权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Plasticity of Electrical Synapses

电突触的可塑性

基本信息

批准号：
1557474
负责人：
Julie Haas
金额：
$ 83.5万
依托单位：
Lehigh University
依托单位国家：
美国
项目类别：
Continuing Grant
财政年份：
2016
资助国家：
美国
起止时间：
2016-04-15 至 2021-03-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1557474&HistoricalAwards=false
关键词：
Plasticity Electrical Synapses

项目摘要

Direct electrical connections between neurons are widespread throughout the mammalian brain, but their contribution to brain function is poorly understood. Similar to other types of connections or so-called synapses between neurons, electrical synapses are known to undergo changes in strength. However, the specific conditions that result in plasticity or changes in strength of electrical synapses are unknown. This project investigates the specific neuronal activity rules and underlying mechanisms whereby these synapses are modified by ongoing brain activity. Further, this project aims to advance our understanding of how these activity-dependent modifications of electrical synapse strength impact brain function, in particular that processing of sensory information via the thalamus to the cortex. The findings will yield important new insights into the function of electrical synapses and their plasticity across the brain, and how the brain gates cortical attention to the sensory environment surrounding the organism. The project involves a combination of brain research, undergraduate and graduate training in neuroscience concepts and research techniques, and educational development through special institutional programs aimed at disadvantaged children and youth, with a goal of public education and broadening participation in science, technology, engineering, and mathematics (STEM disciplines) by traditionally underrepresented students. Learning rules and mechanisms for long-term synaptic modification have been described extensively for neurotransmitter-based synapses. However, strikingly little is yet known about activity-dependent plasticity of electrical synapses, also known as gap junctions. Because electrical synapses are widespread but their importance in mammalian brain function, it is critical that we advance our understanding of whether and how these types of essential synapses are regulated in a use-dependent manner. The central hypothesis of this project is that the strength of electrical synapses in the thalamic reticular nucleus, the major inhibitory regulator of cortico-thalamic communication, is continuously updated by activity in electrically coupled neurons; in turn, this plasticity alters the synchrony within and the inhibitory output of the thalamic reticular nucleus. To test this hypothesis, the control and the impact of electrical synaptic plasticity is investigated using in vitro electrophysiology and optogenetic techniques. Aim 1 examines the mechanisms that underlie plasticity of electrical synapses, with the goal of elucidating and developing predictions about the relationship between activity and synaptic strength. Aim 2 measures the impact of electrical synaptic plasticity on synchrony within networks of coupled thalamic neurons, and thereby offers new insight into the inhibition that coupled interneurons deliver to their downstream targets. Aim 3 tests the functional role of electrical synapse plasticity in brain rhythms and network plasticity. Together, the studies will lead to novel understanding of how electrical synapses contribute to brain function.

神经元之间的直接电连接在整个哺乳动物大脑中广泛存在，但它们对大脑功能的贡献却知之甚少。与神经元之间的其他类型的连接或所谓的突触类似，电突触的强度也会发生变化。然而，导致电突触可塑性或强度变化的具体条件尚不清楚。该项目研究了特定的神经元活动规则和潜在机制，这些突触通过持续的大脑活动而被修改。此外，该项目旨在增进我们对电突触强度的这些活动依赖性修改如何影响大脑功能的理解，特别是通过丘脑到皮质的感觉信息处理。这些发现将为了解电突触的功能及其在大脑中的可塑性，以及大脑如何控制皮层对生物体周围感觉环境的注意力提供重要的新见解。该项目结合了脑研究、神经科学概念和研究技术方面的本科生和研究生培训，以及通过针对弱势儿童和青少年的特殊机构计划进行教育发展，其目标是公共教育和扩大传统上代表性不足的学生对科学、技术、工程和数学（STEM 学科）的参与。对于基于神经递质的突触，长期突触修饰的学习规则和机制已被广泛描述。然而，人们对电突触（也称为间隙连接）的活动依赖性可塑性知之甚少。由于电突触广泛存在，但它们在哺乳动物大脑功能中非常重要，因此我们必须加深对这些类型的重要突触是否以及如何以依赖于使用的方式进行调节的理解至关重要。该项目的中心假设是，丘脑网状核中电突触的强度是皮质丘脑通讯的主要抑制性调节器，通过电耦合神经元的活动不断更新。反过来，这种可塑性改变了丘脑网状核内部的同步性和抑制性输出。为了检验这一假设，使用体外电生理学和光遗传学技术研究了电突触可塑性的控制和影响。目标 1 研究电突触可塑性的机制，目的是阐明并预测活动与突触强度之间的关系。目标 2 测量电突触可塑性对耦合丘脑神经元网络内同步性的影响，从而为耦合中间神经元对其下游目标的抑制提供新的见解。目标 3 测试电突触可塑性在大脑节律和网络可塑性中的功能作用。总之，这些研究将对电突触如何影响大脑功能产生新的理解。