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）： NIND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结构和功能”。在中枢神经系统的神经元中，仍然不太了解SOMA的离子通道如何从树突乔木转化为沿轴突传输的动作势尖峰列车。 该研究项目的总体目标是了解如何在尖峰列车中编码膜电位的统计数据，特别是在动作电位的尖峰输出中，新皮层锥体神经元的体细胞离子通道如何编码有关膜电位的平均值和方差的信息。具体而言，目的是（1）找到离子频道特性，这些特性主要是响应于输入均值而与峰值相反的尖峰，而峰值的结果主要是由于输入波动而导致的，（2）确定平均点火率变化的适应性根据时间变化而变化，该均变化的变化是如何变化的。差异而不是仅使用平均射击率。这些目标将通过开发和应用新颖的理论方法来实现从新皮层大鼠锥体神经元的单个神经元记录获得的数据。 在功能上评估神经元健康的能力将极大地帮助临床治疗从阿尔茨海默氏病到癫痫的神经系统疾病，但目前无法测量神经元的功能健康。在某种程度上，这是因为无法理解神经元传输信息的神经代码。与DMA密码不同，在核酸如何确定蛋白质结构的知识中，人们对中枢神经系统神经元中哪些作用电位的真正含义知之甚少。该项目旨在定义神经法规的一个方面，该方面立即与神经元峰的产生有关，这是神经法规的“字母”。目的是将生物物理特性（例如离子通道密度）与神经元的信息处理联系起来。最终，由于至少可以通过遗传分析确定某些生物物理特性，因此可以使用此类分析来评估患病神经元的功能。