Activity-dependent modification of electrical synapse strength

电突触强度的活动依赖性改变

• 批准号: 8424235
• 负责人: Takao K Hensch
• 金额: $ 8.15万
• 依托单位: HARVARD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8424235
• 关键词: Absence Epilepsy; Action Potentials; Address; Affect; Area; Attention; Attention deficit hyperactivity disorder; Behavioral; Brain; Calcium; Cell Nucleus; Cell membrane; Cells; Cellular Membrane; Charge; Chemical Synapse; Coupled; Cyclic AMP; Disease; Electrical Synapse; Environment; Epilepsy; Fire - disasters; Functional disorder; Gap Junctions; Generations; Goals; Human; In Vitro; Individual; Inhibitory Synapse; Ions; Knowledge; Lead; Learning; Life; Link; Membrane; Methods; Modification; N-Methyl-D-Aspartate Receptors; Neurologic; Neurons; Output; Pattern; Process; Proteins; Research; Role; Sensory; Signal Transduction; Sleep; Sleep Stages; Sodium; Source; Synapses; Synaptic plasticity; Testing; Thalamic structure; Time; Training; alertness; analog; awake; base; connexin 36; field study; insight; neglect; nervous system development; receptor; relating to nervous system; research study; small molecule; transmission process; Absence Epilepsy; Action Potentials; Address; Affect; Area; Attention; Attention deficit hyperactivity disorder; Behavioral; Brain; Calcium; Cell Nucleus; Cell membrane; Cells; Cellular Membrane; Charge; Chemical Synapse; Coupled; Cyclic AMP; Disease; Electrical Synapse; Environment; Epilepsy; Fire - disasters; Functional disorder; Gap Junctions; Generations; Goals; Human; In Vitro; Individual; Inhibitory Synapse; Ions; Knowledge; Lead; Learning; Life; Link; Membrane; Methods; Modification; N-Methyl-D-Aspartate Receptors; Neurologic; Neurons; Output; Pattern; Process; Proteins; Research; Role; Sensory; Signal Transduction; Sleep; Sleep Stages; Sodium; Source; Synapses; Synaptic plasticity; Testing; Thalamic structure; Time; Training; alertness; analog; awake; base; connexin 36; field study; insight; neglect; nervous system development; receptor; relating to nervous system; research study; small molecule; transmission process

DESCRIPTION (provided by applicant): The human process of attention is vital to basic survival and higher learning, yet its basic neurological mechanisms remain poorly understood. During certain stages of sleep and types of epilepsy, the brain is unresponsive to sensory input. The brain center responsible for focusing the neural "searchlight" of attention and for generation spindles during sleep is the thalamic reticular nucleus (TRN), where electrical synapses are a major source of connectivity between neurons in the nucleus. Neurons in the TRN spike in two behaviorally distinct modes - burst and tonic firing - and are densely connected by electrical synapses formed by gap junctions. Gap junctions are a unique type of inter-neuronal connection that physically link membranes of neighboring neurons with small pores, allowing charged ions and small molecules to pass between neurons. These synapses are expressed widely throughout the mammalian brain and are thought to synchronize neuronal activity among coupled neighboring neurons. The strength of electrical synapses, in general, directly affects the synchrony or coherence of connected neurons, and in particular, it modulates the afferent output of the TRN. However, the effect of neuronal activity on electrical synaptic strength has been largely unexplored. We propose two aims that address the fundamental question of how the TRN gates attention by evaluating the role of specific neuronal activity patterns in modifying the strength of electrical synapses in the TRN. In Aim 1, we will record and induce pairings of naturalistic TRN activity patterns - burst and tonic firing - in coupled neurons to determine whether coordinated spiking activity induces changes in electrical synapses. In Aim 2, we will begin to dissect the mechanisms underlying electrical synaptic plasticity by testing whether sodium-based spiking is necessary to induce electrical synaptic modification and by examining the contributions from the prominent low-threshold calcium current in these neurons. Because electrical synapses are widespread throughout the brain, the results of this research will open a promising new field of study and a new perspective on the dynamics of networks that include electrical synapses.

描述（由申请人提供）：人类关注的过程对于基本生存和高等教育至关重要，但其基本神经系统机制仍然很少理解。在睡眠的某些阶段和癫痫类型的类型中，大脑对感觉输入没有反应。丘脑网状核（TRN），负责聚焦注意力和纺锤体的神经“探照灯”的大脑中心，其中电突触是核中神经元之间连通性的主要来源。 TRN尖峰中的神经元在两个行为不同的模式下 - 爆发和滋补 - 并通过间隙连接形成的电气突触密集地连接。间隙连接是一种独特的神经间连接类型，可以将相邻神经元的膜与小毛孔进行物理联系，从而使带电的离子和小分子在神经元之间传递。这些突触在整个哺乳动物大脑中广泛表达，并被认为可以同步耦合的邻近神经元之间的神经元活性。通常，电突触的强度直接影响连接神经元的同步或相干性，尤其是调节TRN的传入输出。然而，神经元活性对电突触强度的影响在很大程度上尚未探索。 我们提出了两个目的，这些目标是通过评估特定神经元活性模式在修改TRN中电气突出强度方面的作用来解决TRN大门如何注意的基本问题。在AIM 1中，我们将记录并诱导耦合神经元中自然主义TRN活性模式的配对 - 爆发和补品射击，以确定协调的尖峰活性是否会导致电气突触的变化。在AIM 2中，我们将通过测试是否需要基于钠的峰值来诱导电突触修饰并检查这些神经元中突出的低阈值钙电流的贡献，从而剖析电突触可塑性的基础机制。由于电气突触在整个大脑中都广泛，因此这项研究的结果将为包括电气突触的网络动力学开辟一个有希望的新研究领域，并有一个新的观点。