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：
8681548
负责人：
Robert C Foehring
金额：
$ 33.5万
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/8681548
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 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 biophysical properties digital hippocampal pyramidal neuron in vivo neocortical neuronal cell body neuronal excitability relating to nervous system spatial integration statistics tool two-photon 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.

描述（由申请人提供）：我们重点关注体感皮层新皮质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，我们将研究新皮质锥体神经元中三种钾通道的功能：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，研究了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。将突触输入转化为尖峰序列是最基本但又极其重要的神经元功能之一。锥体细胞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以及时空结构。为了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，插在大多数突触和主要尖峰生成区之间，但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差距。我们将使用基于数字光处理 (DLP) 的系统或 2 光子显微镜对谷氨酸进行光解笼，以快速、精确地控制锥体细胞树突状谷氨酸受体激活的时空模式和强度。使用这个模拟的生理输入，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 通道如何通过发射率影响整体输入统计数据的编码（“速率编码”），如以及通过精确的尖峰计时（“时间编码”）对单个输入波动进行编码。时间编码对于产生有节奏的皮层活动非常重要，例如在注意力和感觉处理过程中观察到的活动。