Abstract
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.