Computation and adaptation of excitable membranes

描述(由申请人提供)： NINDS宣称的目标是“揭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，胞体的离子通道如何将树突杆上的时变膜电流转化为沿轴突传递的动作电位棘波序列，目前尚不清楚。 这个研究项目的总体目标是了解膜电位的统计是如何在动作电位序列中编码的，特别是新皮质锥体神经元的体细胞离子通道如何编码动作电位的峰输出中膜电位的均值和方差的信息。具体地说，目的是(1)找出主要响应于输入均值而导致尖峰的离子通道特性，而不是主要由于输入波动而导致的尖峰，(2)确定平均激发速率的适应性如何根据时变刺激手段和方差的变化而改变，以及(3)调查跟踪尖峰间隔以编码时变输入手段和方差的效用，而不是仅使用平均激发速率。这些目标将通过开发和应用新的理论方法来获得从大鼠新皮质锥体神经元的单个神经元记录获得的数据来实现。 从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病到癫痫的神经疾病，但目前还没有办法衡量神经元的功能健康。在一定程度上，这是因为人们不理解定义神经元如何传递信息的神经编码；与DMA编码不同，人们对核酸如何决定蛋白质结构知之甚少，而对于中枢神经系统神经元的动作电位真正意味着什么，人们知之甚少。这个项目试图定义神经编码的一个方面，它直接参与神经元棘波的产生，神经元棘波是神经编码的“字母”。其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性质可以从遗传分析中确定，因此使用这种分析来评估患病神经元的功能是可能的。

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.