Plasticity of Electrical Synapses

神经元之间的直接电连接在哺乳动物的大脑中广泛存在，但它们对大脑功能的贡献却知之甚少。与其他类型的连接或神经元之间的所谓突触类似，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，即这些突触被持续的大脑活动所修改。此外，该项目旨在促进我们对这些电突触强度的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层的感觉信息处理。这一发现将对电突触的功能及其在大脑中的可塑性，以及大脑如何将皮层的注意力转移到生物体周围的感觉环境，产生重要的新见解。该项目包括大脑研究、神经科学概念和研究技术的本科和研究生培训，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，目标是公共教育，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。长期突触修饰的学习规则和机制已被广泛描述为基于神经递质的突触。然而，我们对电突触（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，但它们在哺乳动物脑功能中的重要性，因此我们有必要进一步了解这些类型的基本突触是否以及如何以一种依赖于使用的方式进行调节。该项目的中心假设是丘脑网状核中的电突触的强度，皮质-丘脑通讯的主要抑制调节器，通过电偶联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。为了验证这一假设，利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。目的1探讨电突触可塑性的机制，目的是阐明和发展关于活动和突触强度之间关系的预测。目的2测量电突触可塑性对偶联丘脑神经元网络内同步性的影响，从而为偶联中间神经元传递给下游目标的抑制提供新的见解。目的3检验电突触可塑性在脑节律和网络可塑性中的功能作用。总之，这些研究将导致对电突触如何促进大脑功能的新理解。

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.