OPTICAL RECORDING OF SYNAPTIC POTENTIAL INTEGRATION

该提案的长期目标是解释神经细胞的基础 信号处理级别的简单行为形式在所有 功能神经网络的元素。为了实现这个目标，我们将 首先尝试实现动作电位的同时记录和 亚阈值信号在细胞体和突起中都受到限制 使用同时记录脑电活动的制剂的神经元数量 大多数神经元胞体(但不是突起)的动作电位是 已经有可能了。 这项研究将基于使用多点光学记录的实验 技巧。亚阈值电位从小到大变化的光学记录 神经元突起仍然非常困难，因为 相对于噪声的信号大小。目前它只能在大多数情况下使用 有利的实验条件，因此非常有限。的进步。 我们希望获得的敏感性将基于两种方法。第一 我们将利用限制非故意的应用的想法。 电压敏感染料对网络中有限数量的神经元和 而不是玷污整个结构。这可以通过细胞内完成 染料在细胞体中的应用。细胞内染色会改善 光学记录的空间分辨率以及信噪比。 第二，我们建议继续寻找新的染料，以使 无论是细胞外还是细胞内应用，都能获得更好的光信号。我们 建议测试不同类别的最成功染料的类似物 使用几种不同的无脊椎动物 特别适合于光学记录研究的制剂 行为的神经元关联。 有了最佳的染料/制剂组合，我们建议开发 神经元水平上信号整合的记录与分析 功能网络中各个单元的处理过程。我们所了解的知识 了解这些原始动物的正常行为是如何产生的 将帮助我们了解精神障碍，如抑郁症，毒瘾 或者精神分裂症。

The long term goal of the proposal is to explain the neuronal bases of simple forms of behavior at the level of signal processing in all of the elements of the functional neuronal network. Toward this goal, we would first try to achieve simultaneous recording of the action potentials and subthreshold signals in both cell bodies and processes in a restricted number of neurons using preparations in which simultaneous recording of action potentials from most neuronal cell bodies (but not processes)is already possible. This study would be based on experiments using multi-site optical recording techniques. Optical recording of subthreshold potential changes from small neuronal processes is still exceedingly difficult because of the small signal size relative to noise. At present it can only be used under most favorable and thus very limited experimental conditions. The improvement in sensitivity that we hope to obtain will be based on two approaches. First we would exploit the idea of limiting the application of impermeant voltage-sensitive dyes to a restricted number of neurons in the network and not stain the whole structure. This may be accomplished by intracellular application of dyes into cell bodies. Intracellular staining would improve spatial resolution of optical recording as well as signal-to-noise ratio. Second, we propose to continue the search for new dyes that would give better optical signals after either extra- or intracellular application. We propose to test analogs of most successful dyes from different categories of voltage sensitive compounds and to use several different invertebrate preparations that are especially suitable for optical recording studies of neuronal correlates of behavior. With the best dye/preparation combination we then propose to develop the recording and analysis of signal integration at the level of neuronal processes of individual cells within a functional network. The knowledge we obtain about how normal behavior is generated in these primitive animals will help us understand mental disorders such as depression, drug addiction or schizophrenia.