Interaction of Two Neuromodulators in Olfactory Bulb and Cortex

嗅球和皮质中两种神经调节剂的相互作用

• 批准号: 9723947
• 负责人: Michael Hasselmo
• 金额: $ 30.54万
• 依托单位: Harvard University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-15 至 1999-03-01
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9723947&HistoricalAwards=false
• 关键词: Interaction; Two; Neuromodulators; Olfactory; Bulb

Michael E. Hasselmo PROJECT SUMMARY Computer modeling techniques are required to understand how neurochemicals with subtle and broadly distributed effects alter brain function. In the proposed research, computer models of the olfactory system (the brain system for odor perception) will be used to aid in understanding the action of the neurochemicals acetylcholine and norepinephrine on the function of cells can affect the processing of odor memories. OBJECTIVES Research will focus on the following central questions: 1. How do the combined effects of noradrenaline and acetylcholine in the olfactory system affect the capacity of memory? Computer simulations will be used to model two components of the olfactory system: the olfactory bulb and olfactory cortex. Models will be used to analyze how modulation of inhibitory effects by acetylcholine and norepinephrine in the olfactory bulb and cortex increases the number of odor memories that can be stored by allowing them to be coded by separate populations of cells. 2. How does regulation of noradrenaline and acetylcholine in the olfactory system affect behavior in an odor learning task? Computer models will be used to analyze recent behavioral experiments in this laboratory testing how rats respond to odor pairs which share components (odor A with odor B, odor A with odor C) versus how they respond to odor pairs that do not share components (odor A with odor B, odor C with odor D). The model will generate predictions about how the response to odor pairs with shared components should differ depending on whether the response to odor pairs is based on the familiarity of the odor pair, or on whether the odor pair has been paired with a reward. 3. Does acetylcholine more strongly suppress spread of activity at synapses that have been recently increased in strength? Computer models show that storage of odor memories in the olfactory system appears to function more effectively when acetylcholine suppresses the spread of activity at recently strengthened synapses. This prevents recently stored memories from interfering with storage of new memories. In slices of olfactory cortex, we will test whether drugs that activate acetylcholine receptors more strongly suppress spread of activity at synapses which were recently strengthened by repetitive stimulation. 4. Computer models will be used to analyze the effect of acetylcholine and norepinephrine on fast and slow oscillations of activity in the olfactory system. The interaction of oscillations in the olfactory bulb and olfactory cortex will be analyzed, with an emphasis on feedback connections from the olfactory cortex back to the olfactory bulb.

项目总结：要了解具有微妙而广泛影响的神经化学物质如何改变大脑功能，需要计算机建模技术。在提议的研究中，嗅觉系统（气味感知的大脑系统）的计算机模型将被用来帮助理解神经化学物质乙酰胆碱和去甲肾上腺素对细胞功能的作用，这些细胞可以影响气味记忆的处理。研究将集中在以下中心问题：1。去甲肾上腺素和乙酰胆碱在嗅觉系统中的联合作用是如何影响记忆能力的？计算机模拟将用于模拟嗅觉系统的两个组成部分：嗅球和嗅皮层。模型将用于分析乙酰胆碱和去甲肾上腺素在嗅球和皮层中的抑制作用是如何调节的，通过允许它们由不同的细胞群编码来增加可以存储的气味记忆的数量。2. 嗅觉系统中去甲肾上腺素和乙酰胆碱的调节如何影响气味学习任务中的行为？计算机模型将用于分析该实验室最近的行为实验，测试老鼠如何对具有相同成分的气味对（气味A与气味B，气味A与气味C）的反应，以及它们如何对不具有相同成分的气味对（气味A与气味B，气味C与气味D）的反应。该模型将根据对气味对的反应是基于对气味对的熟悉程度，还是基于气味对是否与奖励配对，来预测对具有共享成分的气味对的反应应该如何不同。3. 乙酰胆碱是否更强烈地抑制最近强度增加的突触活动的扩散？计算机模型显示，当乙酰胆碱抑制最近增强的突触活动的扩散时，嗅觉系统中气味记忆的储存似乎更有效。这可以防止最近存储的记忆干扰新记忆的存储。在嗅觉皮层切片中，我们将测试激活乙酰胆碱受体的药物是否会更强烈地抑制突触活动的传播，这些突触最近被重复刺激加强了。4. 计算机模型将用于分析乙酰胆碱和去甲肾上腺素对嗅觉系统活动的快慢振荡的影响。我们将分析嗅球和嗅皮层中振荡的相互作用，重点分析从嗅皮层到嗅球的反馈连接。