RAPID TURNOVER RATE OF THE HIPPOCAMPAL SYNAPTIC NMDA-R1 RECEPTOR SUBUNITS

The decrease in the number of synaptic NMDA receptors produced by prior i.c.v. injections of antisense oligonucleotides was examined in the CA1 stratum radiatum of hippocampal slices. Isolated NMDA and AMPA receptor-mediated components of extracellular synaptic responses were compared in slices obtained from control animals and from animals treated for 48 h with an 18-mer phosphorothioate antisense oligodeoxynucleotide directed against NMDA-R1. In slices ipsilateral to the injected hemisphere, the synaptic NMDA component was decreased by 29% compared with the contralateral side and by 34% compared with animals injected with vehicle alone. At the same time, synaptic AMPA receptor-mediated components were not affected. These results are consistent with a rapid turnover rate of synaptic NMDA-RI and demonstrate the feasibility of antisense oligonucleotide techniques for the depletion of specific synaptic receptor channels.