CELLULAR & COMPUTATIONAL ANALYSIS OF ODOR LEARNING

描述(改编自调查者摘要) 这项建议的长期目标是了解细胞和 长期记忆储存的生化基础，利用气味的储存 陆生软体动物嗅觉系统中的记忆作为模型系统。我们 将测试一个特定的细胞和生物物理模型，以确定主要的中央 陆生最大粘虫体型气味信息处理的位置 气味记忆是空间上分离的神经元带。气味记忆存储器 前脑(PC)叶类似于哺乳动物的嗅球。 有待检验的假设是，嗅觉记忆是由气味识别的 依赖学习的强荧光染料--荧光黄的摄取 PC叶中的神经元组。依赖学习的染料摄取识别 神经元参与存储气味记忆，用于详细的生物物理和 生化分析。拟议工作的具体目标将考验几个 对依赖于学习的染料标记的假设的预测 识别储存气味记忆的神经元。以下是具体的实验 问题将被解决；1.如果弹头被拒绝访问染料标记的 嗅觉训练后，PC叶的神经元是否表现出幼稚的行为 气味记忆功能测试？2.两条染料标记的条带之间的间距 通过学习两种气味产生的气味可以预测辨别能力 在两种习得的气味之间？3.染料标记的神经元在 气味训练通过用训练过的气味刺激选择性地激活？4.做 扰乱PC叶正常神经元活动动力学的药物也 降低气味学习和气味辨别能力？计算模型，该模型 引出的具体实验测试列出的具体目的将是 扩展到包含更具体的细胞生物物理学和 PC叶的神经元连接。我们还将研究细胞机制 学习依赖的染料摄取来开发这种记忆定位工具 在哺乳动物大脑中的应用。生化记忆机制的保守性 而嗅觉系统中的系统设计原则很可能 软体动物神经系统中储存气味记忆的机制将有 与哺乳动物神经系统直接相关。这项工作的结果将是 为开发临床药理学干预措施做出贡献 以记忆功能丧失为主要组成部分的综合症，如精神障碍 发育迟缓和阿尔茨海默氏症。

DESCRIPTION (Adapted from the Investigator's Abstract) The long-term objective of this proposal is to understand the cellular and biochemical basis of long-term memory storage, using the storage of odor memories in the olfactory system of a terrestrial mollusk as a model system. We will test a specific cellular and biophysical model for how the major central site of odor information processing in the terrestrial slug Limax maximus forms odor memories as spatially segregated bands of neurons. The odor memory storage site, the procerebral (PC) lobe, is analogous to the mammalian olfactory bulb. The hypothesis to be tested is that olfactory memories are identified by odor learning-dependent uptake of a highly fluorescent dye, Lucifer yellow, by groups of neurons in the PC lobe. Learning-dependent dye uptake identifies the neurons involved in storing the odor memory for detailed biophysical and biochemical analysis. The specific aims of the proposed work will test several predictions of the hypothesis that the learning-dependent dye labeling identifies neurons storing an odor memory. The following specific experimental questions will be addressed; 1. If the slug is denied access to the dye-labeled neurons in the PC lobe after odor training, does it act naive in a behavioral test of odor memory function? 2. Does the spacing between two dye-labeled bands produced by learning about two odors predict the ability to discriminate between the two learned odors? 3. Are the dye labeled neurons present after odor training selectively activated by stimulation with the trained odor? 4.Do drugs which disrupt normal dynamics of neuronal activity in the PC lobe also degrade odor learning and odor discrimination? The computational model which leads to the specific experimental tests listed in the specific aims will be expanded to incorporate more specific details of the cellular biophysics and neuron connectivity in the PC lobe. We also will study the cellular mechanism of learning-dependent dye uptake to develop this memory localization tool for use in mammalian brain. The conserved nature of biochemical memory mechanisms and system design principles in olfactory systems makes it very likely that mechanisms for odor memory storage in the molluscan nervous system will have direct relevance to the mammalian nervous system. The results of this work will contribute to efforts to develop pharmacological interventions for clinical syndromes in which loss of memory function is a major component, such as mental retardation and Alzheimers disease.