Regulated expression of N-methyl-D-aspartate receptors and associated proteins in teleost electrosensory system and telencephalon.
Several types of N-methyl-D-aspartate (NMDA) receptor-dependent synaptic plasticity are characterized by differences in polarity, induction parameters, and duration, which depend on the interactions of NMDARs with intracellular synaptic and signaling proteins. Here, we examine the NMDAR signaling components in the brain of the weakly electric fish Apteronotus leptorhynchus. Compared with mammalian orthologs, high levels of sequence conservation for known functional sites in both NMDAR subunits (NR1, NR2A-C) and signaling proteins (fyn tyrosine kinase, RasGRF-1 and -2) were found. In situ hybridization analysis demonstrated that, similar to the case in the adult mammal brain, NR2A and NR2B are expressed at moderate levels in most brain regions and at very high levels in the dorsal telencephalon. RasGRF-1 and fyn have a similar distribution and appear to be coexpressed with NR2B in telencephalic regions known to support learning and long-term memory. Both NR2A and NR2B are highly expressed in pyramidal cells of the electrosensory lateral line lobe (ELL) known to exhibit the short-term synaptic plasticity that underlies adaptive feedback cancellation of redundant sensory input. In contrast, nonplastic pyramidal cells expressed only the NR2A subunit. Furthermore, field recordings show that ifenprodil-sensitive NR2B-containing NMDARs predominate for the plastic feedback input to ELL pyramidal cells. However, RasGRF-1 and fyn are expressed only at low levels in a subset of these pyramidal cells. Our data suggest that NMDAR functions are highly conserved between fish and mammals and that synaptic plasticity dynamics in different brain regions are related to the expression patterns of the synaptic signaling proteins interacting with NMDARs.
Harvey-Girard
Erik
E
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada K1H 8M5. erik@apteronote.com
Dunn
Robert J
RJ
Maler
Len
L
D000344:Afferent Pathways / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D017124:Conserved Sequence; D004555:Electric Fish / Q000033:anatomy & histology / Q000378:metabolism*; D019143:Evolution, Molecular; D005246:Feedback / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D008969:Molecular Sequence Data; D009475:Neurons, Afferent / Q000166:cytology / Q000378:metabolism*; D010802:Phylogeny; D051076:Proto-Oncogene Proteins c-fyn / Q000378:metabolism; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D009435:Synaptic Transmission / Q000502:physiology; D013687:Telencephalon / Q000166:cytology / Q000378:metabolism*; D020666:ras-GRF1 / Q000378:metabolism
C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; C513039:RASGRF1 protein, human; D016194:Receptors, N-Methyl-D-Aspartate; D020666:ras-GRF1; D018698:Glutamic Acid; D051076:Proto-Oncogene Proteins c-fyn