Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA receptors.
Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA receptors.
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DOI：
10.1371/journal.pbio.0030354
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发表时间：
2005-11
期刊：
影响因子：
9.8
通讯作者：
Schaefer AT
中科院分区：
文献类型：
--
作者：
Shimshek DR;Bus T;Kim J;Mihaljevic A;Mack V;Seeburg PH;Sprengel R;Schaefer AT
α-氨基-3-羟基-5-甲基-4-异恶唑丙酸酯受体（AMPAR）的遗传扰动被广泛用于剖析感觉编码、学习和记忆的分子机制。在这项研究中，我们研究了钙渗透AMPAR在嗅觉行为中的作用。通过耗尽GluR-B亚基或表达未编辑的GluR-B（Q）获得AMPAR修饰，两者都导致AMPAR的Ca 2+渗透性增加。具有这种功能性AMPAR开关的小鼠，特别是在前脑中，在进行/不进行操作性条件反射任务中表现出增强的嗅觉辨别力和更快的学习能力。然而，嗅觉记忆却严重受损。前脑中GluR-B的耗竭在个体之间是异位可变的（“马赛克”），并且与海马和皮质中的嗅觉记忆下降密切相关。因此，记忆被拯救的转基因GluR-B表达限制在梨状皮质和海马，而增强的气味辨别是独立的GluR-B的变异性和转基因GluR-B的表达。因此，行为和GluR-B表达水平的相关差异允许嗅觉学习，辨别和记忆能力的机械和空间解剖。小鼠前脑中AMPA受体的遗传操纵剖析了梨状皮质和海马中AMPA受体表达变异对嗅觉学习和记忆的特定贡献，而不是辨别力。
Genetic perturbations of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are widely used to dissect molecular mechanisms of sensory coding, learning, and memory. In this study, we investigated the role of Ca2+-permeable AMPARs in olfactory behavior. AMPAR modification was obtained by depletion of the GluR-B subunit or expression of unedited GluR-B(Q), both leading to increased Ca2+ permeability of AMPARs. Mice with this functional AMPAR switch, specifically in forebrain, showed enhanced olfactory discrimination and more rapid learning in a go/no-go operant conditioning task. Olfactory memory, however, was dramatically impaired. GluR-B depletion in forebrain was ectopically variable (“mosaic”) among individuals and strongly correlated with decreased olfactory memory in hippocampus and cortex. Accordingly, memory was rescued by transgenic GluR-B expression restricted to piriform cortex and hippocampus, while enhanced odor discrimination was independent of both GluR-B variability and transgenic GluR-B expression. Thus, correlated differences in behavior and levels of GluR-B expression allowed a mechanistic and spatial dissection of olfactory learning, discrimination, and memory capabilities. Genetic manipulation of AMPA receptors in mouse forebrain dissects specific contributions of AMPA receptor expression variation in piriform cortex and hippocampus to olfactory learning and memory, not discrimination.
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影响因子：
16.2
作者：
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