THE STOCHASTIC NATURE OF SINGLE NEURONS

近年来，许多努力都集中在神经元对突触输入或直接电流注入做出反应的时间精确性上。这种精确度与用于表示和传递信息的神经元编码的性质这一关键问题有关。我们建议通过测量和分析各种噪声源来量化噪声对时间精度的基本限制，这些噪声源包括(I)电压依赖离子通道的随机性质引起的噪声，(Ii)突触背景自发放电的影响和(Iii)突触传递的不可靠、概率性质引入的噪声。1.我们打算使用药物操作来实验地描述新皮质神经元中这些噪声源的特征，从而使我们能够分离单个噪声源如钠、钾或钙通道的贡献。我们将使用单个神经元的胞体和树突的全细胞贴片记录，以及使用红外光学可视化的体外制备的成对连接的神经元。2.我们将冰冻电流噪声反复注入胞体、树突和突触前神经元(使用双电极)，并将噪声记录在突触后电位(阈值下的PSP)以及产生的棘波序列的计时中。这将允许我们计算注入电流和输出尖峰序列之间的互信息。3.我们将把这些测量结果与弱活动线性电缆中的热噪声、通道噪声和突触噪声的分析和数值模型进行比较，这些模型是通过结合这些细胞的详细形态(我们将在细胞内注射生物细胞素后重建)和电生理特性而获得的。4.我们将使用理论技术从噪声源的角度推导出棘波适配度和棘波序列之间的相似性的度量，并将它们与步骤2中获得的实验数据进行比较。我们的研究计划将导致对神经元噪声源的特性及其对单个皮质神经元信息容量的影响的定量描述。

Much effort has focused in recent years on the temporal precision with which neurons respond to synaptic input or to direct current injection. This precision relates to the crucial issue of the nature of the neuronal code used to represent and transmit information. We propose to quantify the fundamental limits that noise places on temporal precision by measuring and analyzing the various noise sources, including (i) noise due to the stochastic nature of voltage-dependent ionic channels, (ii) the effect of "spontaneous" synaptic background firing and (iii) the noise introduced by the unreliable, probabilistic nature of synaptic transmission. 1. We intend to experimentally characterize these noise sources in neocortical neurons using pharmacological manipulations which allow us to isolate the contribution of individual noise sources like Na+, K+ or Ca2+ channels. We will use whole-cell patch recordings at the soma and dendrites of single neurons, and in pairs of connected neurons of an in vitro preparation, visualized using infrared optics. 2. We will repeatedly inject frozen current noise into the soma, the dendrite and the presynaptic neuron (using dual electrodes), and record the noise in the post-synaptic potential (sub-threshold PSPs) as well as the fitter in timing of the resulting spike train. This will allow us to compute the mutual information between the injected current and the output spike train. 3. We will compare these measurements with analytical and numerical models of thermal, channel and synaptic noise in weakly- active linear cables, obtained by incorporating the detailed morphology (that we will reconstruct following infra-cellular injection of biocytin) and the electrophysiological properties of these cells. 4. We will use theoretical techniques to derive measures of spike fitter and similarity between spike trains in terms of the noise sources and compare them against the experimental data obtained in step 2. Our research plan will lead to a quantitative picture of the properties of neuronal noise sources and their effect on the information capacity of individual cortical neurons.