Modulation of dendritic spiking in vivo

体内树突尖峰的调节

• 批准号: 9231511
• 负责人: SPENCER LAVERE SMITH
• 金额: $ 33.25万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-04-01 至 2020-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9231511
• 关键词: Action Potentials; Adaptive Behaviors; Address; Apical; Behavior; Behavioral; Behavioral Assay; Behavioral Mechanisms; Brain; Brain Diseases; Calcium; Complex; Dendrites; Disease; Disinhibition; Distal; Gated Ion Channel; Head; Image; Imaging technology; Interneurons; Ion Channel Gating; Knowledge; Link; Mental disorders; Modeling; Mus; N-Methyl-D-Aspartate Receptors; Neuromodulator; Neurons; Opsin; Patch-Clamp Techniques; Pathologic; Pathway interactions; Play; Process; Publishing; Regulation; Sensory; Shapes; Signal Transduction; Site; Somatostatin; Source; Synapses; System; Techniques; Testing; Transgenic Mice; Vasoactive Intestinal Peptide; Visual; Work; awake; experimental study; hippocampal pyramidal neuron; in vivo; innovation; insight; instrumentation; multiphoton imaging; nervous system disorder; neuronal cell body; neuroregulation; novel therapeutic intervention; optogenetics; patch clamp; permissiveness; public health relevance; somatosensory; two-photon; visual processing; voltage

 DESCRIPTION (provided by applicant): Cortical activity is tightly regulated to support adaptive behavior, but the mechanisms underlying this regulation are unclear. In this project, we will investigate how cortical activity is regulated in vivo, directly at the site of synaptic input Dendrites actively process synaptic input using voltage-gated ion channels and NMDA receptors. We recently showed that these mechanisms support dendritic spiking in awake mice. These dendritic spikes propagate to the soma as depolarizations that can trigger conventional axonal spikes, and thus represent a layer of computational processing that contributes to neuronal selectivity. A recently elucidated circuit motif involving neuromodulation and dendrite-targeting interneurons could play a key role in regulating dendritic spiking during sensory processing and behavior. Here, we use dendritic patch clamp recordings, optogenetics, and new multiphoton imaging technology to interrogate this circuit motif, its effects on dendritic spiking, and its activity during sensory processing and behavior. Since dendritic spiking is an essential component of synaptic integration in cortical circuitry, and dysfunctional synaptic integration is implicated in complex psychiatric and neurological disorders, results from this project can eventually contribute to new therapeutic strategies.

 描述（由适用提供）：皮质活动受到严格的调节以支持适应性行为，但是该法规的基础机制尚不清楚。在该项目中，我们将调查如何直接使用电压门控离子通道和NMDA接收器来积极处理突触输入的突触输入树突位置，如何在体内调节皮质活动。我们最近表明，这些机制支持清醒小鼠中的树突状尖峰。这些树突状尖峰作为depolarisis传播到soma，可以触发常规的轴突尖峰，因此代表了有助于神经选择性的计算过程层。最近阐明的涉及神经调节和树突靶向中间神经元的电路基序在感觉处理和行为过程中可以在注定树突尖峰方面发挥关键作用。在这里，我们使用树突状贴片夹记录，光遗传学和新的多光子成像技术来询问该电路图案，其对树突尖峰的影响及其在感觉处理和行为过程中的活性。由于树突状尖峰是皮质回路中合成整合的重要组成部分，并且在复杂的精神病和神经系统疾病中实施了功能失调的合成整合，因此该项目的结果有时会为新的治疗策略做出贡献。