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Molecular Characterization of NMDA-Like Receptors in Aplysia and Lymnaea: Relevance to Memory Mechanisms

¹ The Whitney Laboratory for Marine Bioscience
² Department of Neuroscience, 9505 Ocean Shore Blvd., St. Augustine, Florida 32080
³ Evelyn F. & William McKnight Brain Institute of the University of Florida, 9505 Ocean Shore Blvd., St. Augustine, Florida 32080

^# To whom correspondence should be addressed. E-mail: moroz{at}whitney.ufl.edu

The N-methyl-D-aspartate (NMDA) receptor belongs to the group of ionotropic glutamate receptors and has been implicated in synaptic plasticity, memory acquisition, and learning in both vertebrates and invertebrates, including molluscs. However, the molecular identity of NMDA-type receptors in molluscs remains unknown. Here, we cloned two NMDA-type receptors from the sea slug Aplysia californica, AcNR1-1 and AcNR1-2, as well as their homologs from the freshwater pulmonate snail Lymnaea stagnalis, LsNR1-1 and LsNR1-2. The cloned receptors contain a signal peptide, two extracellular segments with predicted binding sites for glycine and glutamate, three recognized transmembrane regions, and a fourth hydrophobic domain that makes a hairpin turn to form a pore-like structure. Phylogenetic analysis suggests that both the AcNR1s and LsNR1s belong to the NR1 subgroup of ionotrophic glutamate receptors. Our in situ hybridization data indicate highly abundant, but predominantly neuron-specific expression of molluscan NR1-type receptors in all central ganglia, including identified motor neurons in the buccal and abdominal ganglia as well as groups of mechanosensory cells. AcNR1 transcripts were detected extrasynaptically in the neurites of metacerebral cells of Aplysia. The widespread distribution of AcNR1 and LsNR1 transcripts also implies diverse functions, including their involvement in the organization of feeding, locomotory, and defensive behaviors.

Abbreviations: APV, 2-amino-5-phosphonovalerate • CGC, cerebral giant cells in Lymnaea (MCC homolog) • ER, endoplasmic reticulum • LTP, long-term potentiation • LYC, light yellow cells • MCC, metacerebral cells in Aplysia; NMDA, N-methyl-D-aspartate • NMDAR, ionotropic NMDA-type glutamate receptor • PDZ, acronym from the postsynaptic density 95 (PSD-95), the Drosophila septate junction protein Discs-large and the epithelial tight junction protein ZO-1

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