Computation and adaptation of excitable membranes

描述（由申请人提供）： NINDS的既定目标是“解开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”。“在中枢神经系统的神经元中，仍然没有很好地理解索马的离子通道如何将来自树突状乔木的时变膜电流转换为沿着轴突传输的动作电位尖峰序列。 本研究项目的总体目标是了解膜电位的统计数据是如何编码在尖峰列车，特别是如何体细胞离子通道的新皮层锥体神经元可以编码的平均值和方差的膜电位在动作电位的尖峰输出的信息。具体地，目的是（1）找到导致主要响应于输入均值的尖峰的离子通道特性，与主要由于输入波动而导致的尖峰形成对比，（2）确定平均放电速率的适应如何根据时变刺激均值和方差的变化而变化，以及（3）研究跟踪尖峰间期以编码时变输入均值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，从新皮层大鼠锥体神经元的单神经元记录获得的数据来实现。 功能性评估神经元健康的能力将极大地有助于从阿尔茨海默病到癫痫的神经系统疾病的临床治疗，但目前没有办法测量神经元的功能健康。部分原因是，神经编码（神经元如何传递信息）尚未被理解;与DMA编码不同，DMA编码对核酸如何决定蛋白质结构知之甚多，但对CNS神经元中的动作电位真正含义知之甚少。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”。目标是将生物物理特性（如离子通道密度）与神经元的信息处理直接联系起来。最后，由于至少一些生物物理特性可以从遗传分析中确定，因此可以使用这种分析来评估患病神经元的功能。

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.