Slowly inactivating K+ channels in neocortical pyramidal cells

缓慢失活新皮质锥体细胞中的 K 通道

• 批准号: 8382988
• 负责人: Robert C Foehring
• 金额: $ 36.72万
• 依托单位: UNIVERSITY OF TENNESSEE HEALTH SCI CTR
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-03-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8382988
• 关键词: Action Potentials; Affect; Anesthesia procedures; Anesthetics; Animals; Anoxia; Apical; Apoptosis; Attention; Axon; Cells; Central Nervous System Diseases; Code; Dendrites; Detection; Development; Disease; Epilepsy; Foundations; Functional disorder; Generations; Glutamate Receptor; Glutamates; Grant; In Vitro; Individual; Ion Channel; Kinetics; Knowledge; Kv2.1 channel; Learning; Learning Disorders; Light; Link; Mediating; Membrane; Membrane Potentials; Memory; Methodology; Microscopy; Molecular; Neurons; Noise; Output; Pattern; Photons; Physiological; Play; Potassium Channel; Preparation; Process; Property; Pyramidal Cells; Receptor Activation; Rodent; Role; Sensory Process; Signal Transduction; Simulate; Site; Somatosensory Cortex; Spain; Stimulus; Stroke; Structure; Synapses; System; Testing; Time; Training; Voltage-Gated Potassium Channel; Work; base; digital; hippocampal pyramidal neuron; in vivo; neocortical; neuronal cell body; neuronal excitability; relating to nervous system; spatial integration; statistics; tool; voltage

DESCRIPTION (provided by applicant): We focus on the functional consequences of voltage-gated potassium channel (Kv) diversity in neocortical pyramidal cells from somatosensory cortex. Specifically, we will study the functions of three types of potassium channels in neocortical pyramidal neurons: Kv1, Kv2, and Kv7 channels. The proposed studies go beyond the standard notion that potassium channels act as an intrinsic brake on excitability to studying the effects of these channels on the types of information that pyramidal cells respond to and how those inputs are transformed into trains of action potentials. Transformation of synaptic inputs into spike trains is one of the most basic and yet fundamentally important neuronal functions. Both the rate and timing of action potentials in pyramidal cells are important for cortical function, and both depend on the intensity and the spatial and temporal structure of the synaptic input to each neuron. A better understanding of the roles of particular ion channels requires tests under conditions relevant for behaving animals, yet such information is very limited at present. Neuronal dendrites are nonlinear processors, and are interposed between most synapses and the primary spike generating zone, but the effects of distributed input to dendrites on spike output remain a huge gap in our experimental understanding of single-neuron computation. We will use photo uncaging of glutamate with a digital light processing (DLP)-based system or 2-photon microscopy to rapidly and precisely control the spatio-temporal pattern and intensity of dendritic glutamate receptor activation to pyramidal cells. Using this simulated physiological input, we will investigate how the effects of Kv channels (Kv1, Kv2, Kv7) depend on the input statistics and how these Kv channels affect the encoding of overall input statistics by firing rate ("rate coding"), as well as the encoding of individual inpu fluctuations by precise spike timing ("time coding"). Time coding is important for generation of rhythmic cortical activity such as observed during attention and sensory processing. PUBLIC HEALTH RELEVANCE: Knowing the detailed functions of particular K channels is essential to understanding how neurons process inputs into spike outputs and for developing more specific disease therapies. Alterations of K channel function (e.g., reduction of Kv1 or Kv7 expression) leads to pathophysiology such as epilepsy. Kv2 channels play important roles in the homeostatic suppression of neuronal hyperexcitability under pathological conditions, mediate apoptosis in PCs exposed to anoxia, and are targets of anesthetics.

描述（由申请人提供）：我们专注于体感皮层新皮层锥体细胞中电压门控钾通道（Kv）多样性的功能后果。具体来说，我们将研究三种类型的钾通道在新皮层锥体神经元的功能：Kv1，Kv2和Kv7通道。拟议的研究超越了钾通道作为兴奋性内在制动器的标准概念，以研究这些通道对锥体细胞响应的信息类型的影响以及这些输入如何转化为动作电位序列。将突触输入转化为锋电位序列是神经元最基本的功能之一。锥体细胞中动作电位的速率和时间对于皮质功能都很重要，并且都取决于每个神经元突触输入的强度和时空结构。要更好地了解特定离子通道的作用，需要在与动物行为相关的条件下进行测试，但目前此类信息非常有限。神经元树突是一种非线性处理器，介于大多数突触和主要的尖峰产生区之间，但是树突的分布式输入对尖峰输出的影响在我们对单神经元计算的实验理解中仍然存在巨大的差距。我们将使用基于数字光处理（DLP）的系统或双光子显微镜的谷氨酸的光解开，以快速和精确地控制树突状谷氨酸受体激活锥体细胞的时空模式和强度。使用这种模拟的生理输入，我们将研究Kv通道（Kv1，Kv2，Kv7）的影响如何依赖于输入统计，以及这些Kv通道如何影响整体输入统计的编码（“速率编码”），以及编码的个人输入波动精确的尖峰定时（“时间编码”）。时间编码对于产生有节奏的皮层活动很重要，例如在注意力和感觉处理过程中观察到的。 公共卫生关系：了解特定K通道的详细功能对于理解神经元如何将输入处理为尖峰输出以及开发更具体的疾病疗法至关重要。K通道功能的改变（例如，Kv1或Kv7表达的减少）导致病理生理学，例如癫痫。Kv2通道在病理条件下对神经元过度兴奋的稳态抑制中起重要作用，介导暴露于缺氧的PC的凋亡，并且是麻醉剂的靶点。