NMDA/R1-antisense oligonucleotide influences the early stage of long-term potentiation in the CA1-region of rat hippocampus.
We have studied the role of the N-methyl-D-aspartate (NMDA)/R1 receptor subunit in the mechanism of long-term potentiation (LTP) using an antisense-oligodeoxynucleotide strategy. Antisense-oligodeoxynucleotide (aDON; 10 nmol) or sense-oligodeoxynucleotide (sDON) were applied into the right ventricle of 7 week old male Wistar rats every 12 h for 3 days. Thereafter, in hippocampal slices extracellular field potential recordings were made from the CA1 region. LTP was induced by tetanization of the Schaffer collaterals. In slices of rats pretreated with aDON the initial potentiation of the population spike (POP-spike) was significantly smaller than in those from saline controls and naive animals. The impairment of potentiation lasted for about 50 min posttetanus. However, the potentiation of the field excitatory postsynaptic potentials (fEPSPs) was significantly influenced for 15 min. In slices of rats pretreated with sDON only a small, insignificant difference in POP-spike and fEPSP potentiation was seen compared to saline controls. In the group pretreated with aDON the specific binding of [3H]glutamate to the NMDA-receptor subtype of hippocampal membranes was reduced to about 63% in comparison with the group treated with sDON. These results indicate that DONs reached the target region when applied intraventricularly and were able to suppress the translation of mRNA of the NMDA/R1 receptor subunit. They further support the assumption of the essential role of the NMDA/R1 receptor subunit in the induction of LTP.
Matthies
H
H
Institute of Pharmacology and Toxicology, Otto von Guericke University, Magdeburg, Germany. matthies@medizin.uni-magdeburg.de
Schröder
H
H
Wagner
M
M
Höllt
V
V
Krug
M
M
D000818:Animals; D001483:Base Sequence; D004594:Electrophysiology; D018698:Glutamic Acid / Q000378:metabolism / Q000494:pharmacology; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology*; D008297:Male; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics* / Q000648:ultrastructure; D013997:Time Factors; D014316:Tritium
D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D014316:Tritium; D018698:Glutamic Acid