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

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）：人类的注意力过程对于基本生存和高等教育至关重要，但其基本神经机制仍然知之甚少。在睡眠的某些阶段和癫痫类型期间，大脑对感觉输入没有反应。丘脑网状核（TRN）负责集中注意力的神经“探照灯”并在睡眠期间生成纺锤体，其中电突触是核中神经元之间连接的主要来源。 TRN 中的神经元以两种行为不同的模式（爆发和强直放电）尖峰，并通过间隙连接形成的电突触紧密连接。间隙连接是一种独特的神经元间连接类型，它通过小孔将相邻神经元的膜物理连接起来，允许带电离子和小分子在神经元之间通过。这些突触在整个哺乳动物大脑中广泛表达，并被认为可以同步相邻神经元之间的神经元活动。一般来说，电突触的强度直接影响连接神经元的同步性或一致性，特别是它调节 TRN 的传入输出。然而，神经元活动对电突触强度的影响在很大程度上尚未被探索。 我们提出了两个目标，通过评估特定神经元活动模式在改变 TRN 电突触强度中的作用来解决 TRN 如何控制注意力的基本问题。在目标 1 中，我们将记录并诱导耦合神经元中自然 TRN 活动模式的配对（爆发和强直放电），以确定协调的尖峰活动是否会引起电突触的变化。在目标 2 中，我们将开始剖析电突触可塑性的机制，通过测试钠基尖峰是否是诱导电突触修饰所必需的，并检查这些神经元中突出的低阈值钙电流的贡献。由于电突触广泛存在于整个大脑中，这项研究的结果将开辟一个有前景的新研究领域，并为包括电突触的网络动力学提供新的视角。

项目成果

State-dependent modulation of gap junction signaling by the persistent sodium current.

• DOI: 10.3389/fncel.2011.00031
• 发表时间: 2011
• 期刊: Frontiers in cellular neuroscience
• 影响因子: 5.3
• 作者: Haas JS;Landisman CE
• 通讯作者: Landisman CE

Bursts modify electrical synaptic strength.

• DOI: 10.1016/j.brainres.2012.05.061
• 发表时间: 2012-12-03
• 期刊: Brain research
• 影响因子: 2.9
• 作者: Haas JS;Landisman CE
• 通讯作者: Landisman CE