在脊椎動物中，NMDA接受器在參與突觸的可塑性以及記憶的形成過程中扮演著重要的調控角色。然而，有關非脊椎動物NMDA接受器的研究，至今闕如。在果蠅基因體中已知包含兩種參與組成NMDA接受器次單位的基因□dNR1和dNR2. 將兩者共同表現在非洲爪蟾的卵中(Xenopus oocyte) 可以藉由glutamate 或NMDA引發流入的電流，產生電位的改變。本文中也發現NMDA接受器在成蟲果蠅中參與著學習與長期記憶的形成。利用免疫螢光標示的方法，觀察果蠅NMDA接受器中的兩種次單位在果蠅腦中的分佈狀況，證實在成蟲的果蠅中， dNR1與dNR2微弱的表現在整個腦中，但明顯的表現在腦中的數個細胞，並且其中一些細胞圍繞著蕈狀體(Mushroom body)的突觸區(dendritic region)。利用弱顯型的(hypomorphic) dNR1突變株，在同型合子的(homozygous) dNR1突變株中輕微的抑制dNR1表現。在行為研究上，則觀察到其嗅覺學習的缺陷。這些現象皆可以藉由再表現正常的dNR1得以回復。我也發現，藉由熱休克操縱子的控制，可在成蟲階段，大量誘導表現dNR1-antisense，則見到dNR1的表現被顯著抑制，同時造成嗅覺學習缺陷，這些果蠅顯示抑制dNR1也會影響LTM。另外，本文也建構UAS-dNR2與UAS-RNAidNR2基因轉殖果蠅。並同時利用泛神經表現的elav-Gal4果蠅株，控制UAS-RNAidNR2的表現。這些操作則顯示抑制dNR2的表現也同樣會影響果蠅的嗅覺學習。利用UAS-dNR2-2在上述的控制下，大量表現dNR2-2，會提升學習後24小時的長期記憶表現。我又利用適當的Gal4果蠅株，驅動dNR2-2以表現在腦中特殊的部位，如此已初步證實，ellipsoid body的大量表現的dNR2-2，增強了果蠅學習後的LTM。這些結果證實NMDA接受器參與果蠅記憶的形成，在非脊椎動物仍具有在脊椎動物中的相同執行記憶可塑性(memory plasticity)功能的角色。

It is well known that NMDA receptors (N-methyl-D-asparate; NMDARs or NRs) are essential in the regulation of synaptic and behavioral plasticity in vertebrates. In the Drosophila genome, two NMDAR homologs, dNR1 and dNR2 have been reported. Dosage- and voltage-dependent Glutamate and NMDA induced inward currents have been shown when they are co-expressed in Xenopus oocytes. In this study, I demonstrate the existence of functional NMDARs and their acute requirement for learning and long-term memory in the brain of adult Drosophila. Immunohistochemical labels indicate that two subtypes of NMDAR protein are weakly expressed in the entire brain, but with a preference in some neurons surrounding the dendritic region of the mushroom bodies. I show that hypomorphic mutations of the essential dNR1 gene disrupt olfactory learning, and can be rescued by wild-type transgenes. I also find that acute induction of an antisense mRNA for dNR1 disrupts olfactory learning and long-term memory (LTM), indicating a functional role for dNR1 in the formation of associative memory in Drosophila. Consistently, the knocking down of dNR2 protein by expressing UAS-RNAidNR2 under a pan-neuronal driver (elav-Gal4) also disrupts olfactory learning. In contrast, increasing dNR2 protein enhances LTM. Surprisingly, the dNR2-2 may act in the ellipsoid body, instead of the mushroom body, neurons for the LTM enhancement. These data explicitly demonstrate the involvement of NMDAR in Drosophila memory; further establish a role of NMDAR in the memory plasticity which has been preserved in evolution.

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