Department of Life Science, National Tsing Hua University, Hsinchu 30013, Taiwan.
Proc Natl Acad Sci U S A. 2011 Aug 16;108(33):13794-9. doi: 10.1073/pnas.1019483108. Epub 2011 Aug 1.
Pavlovian olfactory learning in Drosophila produces two genetically distinct forms of intermediate-term memories: anesthesia-sensitive memory, which requires the amnesiac gene, and anesthesia-resistant memory (ARM), which requires the radish gene. Here, we report that ARM is specifically enhanced or inhibited in flies with elevated or reduced serotonin (5HT) levels, respectively. The requirement for 5HT was additive with the memory defect of the amnesiac mutation but was occluded by the radish mutation. This result suggests that 5HT and Radish protein act on the same pathway for ARM formation. Three supporting lines of evidence indicate that ARM formation requires 5HT released from only two dorsal paired medial (DPM) neurons onto the mushroom bodies (MBs), the olfactory learning and memory center in Drosophila: (i) DPM neurons were 5HT-antibody immunopositive; (ii) temporal inhibition of 5HT synthesis or release from DPM neurons, but not from other serotonergic neurons, impaired ARM formation; (iii) knocking down the expression of d5HT1A serotonin receptors in α/β MB neurons, which are innervated by DPM neurons, inhibited ARM formation. Thus, in addition to the Amnesiac peptide required for anesthesia-sensitive memory formation, the two DPM neurons also release 5HT acting on MB neurons for ARM formation.
在果蝇中，巴甫洛夫式嗅觉学习产生了两种具有遗传差异的中期记忆形式：麻醉敏感记忆，需要失忆基因；麻醉抗性记忆（ARM），需要萝卜基因。在这里，我们报告说，ARM 在血清素（5-HT）水平升高或降低的果蝇中分别得到特异性增强或抑制。5-HT 的需求与失忆突变的记忆缺陷具有加性，但被萝卜突变所掩盖。这一结果表明，5-HT 和 Radish 蛋白在 ARM 形成的同一途径上起作用。有三条支持性证据表明，ARM 的形成需要 5-HT 仅从两个背侧配对中侧（DPM）神经元释放到蘑菇体（MBs）上，MBs 是果蝇的嗅觉学习和记忆中心：（i）DPM 神经元对 5-HT 抗体呈免疫阳性；（ii）DPM 神经元中 5-HT 合成或释放的时间抑制，但不是其他血清素能神经元，损害了 ARM 的形成；（iii）敲低α/β MB 神经元中 d5HT1A 血清素受体的表达，这些神经元被 DPM 神经元支配，抑制了 ARM 的形成。因此，除了形成麻醉敏感记忆所需的失忆肽外，这两个 DPM 神经元还释放 5-HT，作用于 MB 神经元以形成 ARM。
