OPTICAL RECORDING OF SYNAPTIC POTENTIAL INTEGRATION

突触电位整合的光学记录

• 批准号: 3414957
• 负责人: LAWRENCE B COHEN
• 金额: $ 6.1万
• 依托单位: YALE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1990
• 资助国家: 美国
• 起止时间: 1990-09-01 至 1993-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3414957
• 关键词: Mollusca; axon; cell cell interaction; dendrites; electrical potential; electrophysiology; fluorescent dye /probe; ganglions; neural information processing; neurons; neuropsychology; saltwater environment; single cell analysis; soma; synapses

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.

该提案的长期目标是解释神经元基础 所有信号处理级别的简单行为形式 功能神经元网络的元素。为了这个目标，我们将 首先尝试实现动作电位的同时记录 细胞体和过程中的阈下信号在有限的范围内 使用同时记录的制剂的神经元数量 大多数神经元细胞体（但不是过程）的动作电位是 已经可能了。 这项研究将基于使用多站点光学记录的实验 技术。光学记录亚阈值电位变化从小到大 由于神经元过程很小，因此神经元过程仍然非常困难 相对于噪声的信号大小。目前只能在大多数情况下使用 有利且因此非常有限的实验条件。改进之处在于 我们希望获得的敏感性将基于两种方法。第一的 我们将利用限制非渗透性应用的想法 对网络中有限数量的神经元进行电压敏感染料， 不弄脏整个结构。这可以通过细胞内 将染料应用到细胞体中。细胞内染色会改善 光学记录的空间分辨率以及信噪比。 其次，我们建议继续寻找新的染料，以提供 在细胞外或细胞内应用后可获得更好的光信号。我们 建议测试不同类别的最成功染料的类似物 电压敏感化合物并使用几种不同的无脊椎动物 特别适合光学记录研究的制剂 行为的神经元相关性。 通过最佳的染料/制剂组合，我们建议开发 神经元水平信号整合的记录和分析 功能网络内单个细胞的过程。我们的知识 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疾病，如抑郁症、毒瘾 或精神分裂症。