THE STOCHASTIC NATURE OF SINGLE NEURONS

近年来，许多努力集中在神经元对突触输入或直流电注入的响应的时间精度上。这种精确性与用来表示和传递信息的神经元代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）由于电压依赖性离子通道的随机性而产生的噪声;（ii）“自发”突触背景放电的影响;以及（iii）突触传递的不可靠性和概率性所引入的噪声。1.我们打算用药理学操作，使我们能够隔离如Na+，K+或Ca 2+通道的个别噪声源的贡献，在新皮层神经元的实验特性，这些噪声源。我们将在单个神经元的索马和树突处使用全细胞贴片记录，并在体外制备的成对连接的神经元中使用红外光学可视化。2.我们将重复地将冻结的电流噪声注入索马、树突和突触前神经元（使用双电极），并记录突触后电位（亚阈值PSP）中的噪声以及所得尖峰序列的定时。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.我们将这些测量与热，通道和突触噪声的分析和数值模型进行比较弱活性线性电缆，通过将详细的形态学（我们将重建以下细胞内注射生物胞素）和这些细胞的电生理特性。4.我们将使用理论技术来获得尖峰拟合和尖峰序列之间的噪声源的相似性的措施，并将它们与步骤2中获得的实验数据进行比较。我们的研究计划将定量了解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。

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.