Abstract
Drosophila genome displays two NMDA receptor (NR) subunit homologous genes, dNR1 and dNR2. We have previously found that either dNR1 or dNR2 is essential for functional NMDA receptors. Because Mg2+ block of the NR is released by depolarization of the postsynaptic cell, NRs has been considered as a coincidence detector for correlated synaptic inputs and may be crucial for learning acquisition. However, interestingly, Drosophila mutant for dNR1 showed severe disruption in protein-synthesis-dependent long-term memory (LTM) but not much in acquisition (LRN) after olfactory Pavlovian conditioning. Ion blockade of glutamate receptors are governed by residue located at the apex of the M2 loop that is called the N/Q site. The NR subunits have Asn (N) residue at the N/Q site, whereas non-NMDA (AMPA and kainate) receptors which do not show Mg2+ block have Gln (Q) residue at this site. In contrast to mammalian NR subunits and dNR1, N/Q site of dNR2 is occupied by Q. Despite of this N/Q site of dNR2, NMDA receptors formed in combination of dNR1 and dNR2 exhibited significant Mg2+ block property under physiological Mg2+ concentration (20 mM). When N/Q site of dNR1 was substituted to Q from N, dNRs consist of mutated dNR1 (dNR1-N631Q) and dNR2 did not display the Mg2+ block property. Similar to dNR1 mutant, transgenic flies overexpressing dNR1-N631Q in neuronal cells displayed significant impairment in LTM but not in LRN. These results suggest that Mg2+ block of NRs are important for LTM but not in acquisiton [Jpn J Physiol 55 Suppl:S137 (2005)]
