Slowly inactivating K+ channels in neocortical pyramidal cells

缓慢失活新皮质锥体细胞中的 K 通道

基本信息

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
项目类别：
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

项目摘要

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）：我们关注来自体感皮质的新皮层金字塔细胞中电压门控通道（KV）多样性的功能后果。具体而言，我们将研究新皮层锥体神经元中三种类型的钾通道的功能：KV1，KV2和KV7通道。拟议的研究超出了标准概念，即钾通道充当兴奋性的内在制动器，以研究这些通道对金字塔细胞响应的信息类型以及如何将这些输入转化为动作电位的信息。将突触输入转化为尖峰列车是最基本但根本上重要的神经元功能之一。锥体细胞中作用电位的速率和时机对于皮质功能都很重要，并且都取决于突触输入的强度和空间和时间结构对每个神经元。更好地了解特定离子通道的作用需要在与行为动物相关的条件下进行测试，但目前此类信息非常有限。神经元树突是非线性处理器，并且在大多数突触和主要的尖峰生成区之间插入，但是分布式输入对树突对峰值输出的影响仍然是我们对单神经计算的实验理解的巨大差距。我们将使用具有数字光处理（DLP）的系统或2光子显微镜的谷氨酸光渗透来迅速，精确地控制时空模式以及树突状谷氨酸受体激活对锥体细胞的强度。使用此模拟的生理输入，我们将研究KV通道（KV1，KV2，KV7）的影响如何取决于输入统计数据以及这些KV通道如何通过触发率（“速率编码”）来影响整体输入统计的编码，以及通过精确的Spike Spike Spike Timing Timeging（Time Sigeing（Time Sigeing）（'）。时间编码对于产生有节奏的皮质活性很重要，例如在注意力和感觉处理过程中观察到。公共卫生相关性：了解特定K通道的详细功能对于了解神经元如何处理尖峰输出和开发更特定的疾病疗法至关重要。 K通道功能的改变（例如，KV1或KV7表达的还原）导致病理生理学，例如癫痫。 KV2通道在病理条件下神经元过度刺激性的稳态抑制中起着重要作用，介导暴露于缺氧的PC中的凋亡，并且是麻醉药的靶标。