Interaction of Two Neuromodulators in Olfactory Bulb and Cortex

Michael E.哈塞尔莫 需要计算机建模技术来了解具有微妙和广泛分布影响的神经化学物质如何改变大脑功能。 在拟议的研究中，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，可以影响气味记忆的处理。 研究将集中在以下中心问题：1。嗅觉系统中去甲肾上腺素和乙酰胆碱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。 模型将用于分析嗅球和皮层中乙酰胆碱和去甲肾上腺素的抑制作用的调制如何增加气味记忆的数量，这些记忆可以通过允许它们由单独的细胞群体编码来存储。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本实验室最近的行为实验，测试大鼠如何对共享组分的气味对（气味A与气味B，气味A与气味C）作出反应，以及它们如何对不共享组分的气味对（气味A与气味B，气味C与气味D）作出反应。 该模型将生成关于对具有共享成分的气味对的反应如何不同的预测，这取决于对气味对的反应是基于对气味对的熟悉度，还是基于气味对是否与奖励配对。3.乙酰胆碱是否更强烈地抑制了最近强度增加的突触活动的传播？ 计算机模型显示，当乙酰胆碱抑制了最近加强的突触活动的传播时，嗅觉系统中气味记忆的储存似乎更有效地发挥作用。 这防止了最近存储的记忆干扰新记忆的存储。在嗅觉皮层的切片中，我们将测试激活乙酰胆碱受体的药物是否更强烈地抑制最近通过重复刺激加强的突触活动的传播。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速和缓慢振荡的影响。 在嗅球和嗅觉皮层的振荡的相互作用将被分析，从嗅觉皮层反馈回嗅球的连接的重点。

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.