Appetitive learning requires the alpha1-like octopamine receptor OAMB in the Drosophila mushroom body neurons.
Appetitive learning requires the alpha1-like octopamine receptor OAMB in the Drosophila mushroom body neurons.
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DOI：
10.1523/jneurosci.3042-12.2013
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发表时间：
2013-01-23
期刊：
影响因子：
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通讯作者：
Han KA
中科院分区：
文献类型：
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作者：
Kim YC;Lee HG;Lim J;Han KA
联想学习是行为可塑性的一种基本形式。章鱼胺在无脊椎动物的各种学习类型中起着核心作用，然而其靶受体和潜在机制尚不清楚。果蝇提供了一个强大的系统来揭示学习和记忆的机制。在这里，我们报道了蘑菇体神经元中的OAMB介导章鱼胺的食欲嗅觉学习信号。章鱼胺受体OAMB有两种异构体（OAMB- k3和OAMB- as），在第三细胞质环和下游序列上有所不同。每个OAMB异构体的激活会增加细胞内Ca2+，类似于α 1肾上腺素能受体，而OAMB- k3也会刺激cAMP的产生。在测试果蝇学习和记忆与糖奖励有关的气味的能力时，oamnull突变体在食欲嗅觉条件反射方面表现出严重受损。这种缺陷也出现在蘑菇体中OAMB表达减少的半胚突变体中，蘑菇体是嗅觉调节的关键大脑结构。与此一致的是，在蘑菇体αβ和γ神经元中条件表达oamb亚型可以完全恢复oamb突变体的学习表型。这些结果表明，OAMB受体是介导章鱼胺的食欲嗅觉学习信号的关键分子，其功能位点为蘑菇体αβ和γ神经元。本研究在理解细胞机制和神经回路调节奖励性学习和记忆方面迈出了重要的一步。
Associative learning is a fundamental form of behavioral plasticity. Octopamine plays central roles in various learning types in invertebrates, however the target receptors and underlying mechanisms are poorly understood. Drosophila provides a powerful system to uncover the mechanisms for learning and memory. Here, we report that OAMB in the mushroom body neurons mediates the octopamine’s signal for appetitive olfactory learning. The octopamine receptor OAMB has two isoforms (OAMB-K3 and OAMB-AS), differing in the third cytoplasmic loop and downstream sequence. The activation of each OAMB isoform increases intracellular Ca2+ similar to the alpha1 adrenergic receptor, while OAMB-K3 additionally stimulates cAMP production. The oamb null mutants showed severely impaired learning in appetitive olfactory conditioning that tests flies’ capacity to learn and remember the odor associated with sugar reward. This deficit was also seen in the hypomorphic mutant with reduced OAMB expression in the mushroom bodies, the brain structure crucial for olfactory conditioning. Consistently, the oamb mutant’s learning phenotype was fully rescued by conditional expression of either OAMB isoform in the mushroom body αβ and γ neurons. These results indicate that the OAMB receptor is a key molecule mediating the octopamine’s signal for appetitive olfactory learning and its functional site is the mushroom body αβ and γ neurons. This study represents a critical step forward in understanding the cellular mechanism and neural circuit mediating reward learning and memory.