Computation and adaptation of excitable membranes

可兴奋膜的计算和适应

• 批准号: 7478480
• 负责人: Brian Nils Lundstrom
• 金额: $ 3.96万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-16 至 2011-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7478480
• 关键词: Accounting; Action Potentials; Alzheimer' s Disease; Axon; Brain; Characteristics; Classification; Clinical Treatment; Code; Data; Dendrites; Dependence; Detection; Epilepsy; Experimental Models; Goals; Health; Hodgkin Disease; In Vitro; Ion Channel; Lead; Letters; Measures; Membrane; Membrane Potentials; Modeling; National Institute of Neurological Disorders and Stroke; Neurons; Nucleic Acids; Output; Pathway interactions; Positioning Attribute; Production; Property; Rattus; Research Project Grants; Signal Transduction; Stimulus; Structure; System; Testing; Theoretical model; Time; Training; Visual system structure; Work; analog; base; density; detector; fly; genetic analysis; hippocampal pyramidal neuron; information processing; neocortical; nervous system disorder; neuronal cell body; novel; protein structure; relating to nervous system; response; statistics

DESCRIPTION (provided by applicant): Stated goals of the NINDS are to "unravel the complexities of information transfer within the brain" and encourage "further study of ion channel structure and function." In neurons of the CNS, it is still not well understood how ion channels of the soma convert time-varying membrane currents from the dendritic arbor into action potential spike trains that are transmitted along axons. The overall goal of this research project is to understand how statistics of membrane potentials are encoded in spike trains and specifically how somatic ion channels of a neocortical pyramidal neuron can encode information about the mean and variance of the membrane potential in the spiking output of action potentials. Specifically, the aims are to (1) find ion channel characteristics that lead to spiking primarily in response to the input mean in contrast to spiking that results primarily due to input fluctuations, (2) determine how the adaptation of the mean firing rate changes according to changes in the time-varying stimulus means and variances, and (3) investigate the utility of keeping track of interspike intervals to code for time-varying input means and variances instead of using only the mean firing rate. These aims will be accomplished by developing and applying novel theoretical approaches to data obtained from single neuron recordings of neocortical rat pyramidal neurons. The ability to functionally assess the health of a neuron would greatly assist in clinical treatment of neurological disorders from Alzheimer's disease to epilepsy, but there is currently no way to measure a neuron's functional health. In part, this is because the neural code, which defines how neurons transmit information, is not understood; unlike the DMA code, where much is known about how nucleic acids determine protein structure, little is known about what action potentials in CNS neurons really mean. This project seeks to define an aspect of the neural code that is immediately involved in the production of neuronal spikes, which are the "letters" of the neural code. The goal is to directly relate biophysical properties such as ion channel densities to the information processing that the neuron does. Eventually, since at least some biophysical properties may be determined from genetic analyses, it may be possible to use such analyses to evaluate the function of diseased neurons.

描述（由申请人提供）： NINDS 的既定目标是“揭示大脑内信息传递的复杂性”并鼓励“进一步研究离子通道的结构和功能”。在中枢神经系统神经元中，目前尚不清楚体细胞的离子通道如何将来自树突乔木的时变膜电流转换为沿轴突传输的动作电位尖峰序列。 该研究项目的总体目标是了解膜电位的统计数据如何在尖峰序列中编码，特别是新皮质锥体神经元的体细胞离子通道如何编码有关动作电位尖峰输出中膜电位均值和方差的信息。具体来说，目标是 (1) 找到主要响应于输入平均值而导致尖峰的离子通道特征，与主要由于输入波动而导致的尖峰相反，(2) 确定平均放电率的适应如何根据输入变化而变化随时间变化的刺激手段和方差的变化，以及（3）研究跟踪峰间间隔以编码随时间变化的输入手段和方差而不是仅使用平均放电率的效用。这些目标将通过开发和应用新的理论方法来实现，这些方法是从新皮质大鼠锥体神经元的单个神经元记录中获得的数据。 功能评估神经元健康状况的能力将极大地有助于从阿尔茨海默病到癫痫等神经系统疾病的临床治疗，但目前还没有办法测量神经元的功能健康状况。部分原因是，定义神经元如何传递信息的神经代码尚未被理解。与 DMA 代码不同的是，我们对核酸如何决定蛋白质结构了解甚多，但我们对 CNS 神经元动作电位的真正含义知之甚少。该项目旨在定义神经代码的一个方面，该方面直接参与神经元尖峰的产生，神经元尖峰是神经代码的“字母”。目标是将离子通道密度等生物物理特性与神经元进行的信息处理直接联系起来。最终，由于至少一些生物物理特性可以通过遗传分析来确定，因此可以使用此类分析来评估患病神经元的功能。