The Journal of Neurophysiology Vol. 83 No. 1 January 2000, pp. 616-620
Copyright ©2000 by the American Physiological Society

Fast NMDA Receptor-Mediated Synaptic Currents in Neurons From Mice Lacking the 2 (NR2B) Subunit

Vollum Institute, Oregon Health Sciences University, Portland, Oregon 97201-3098

Tovar, Kenneth R., Kathleen Sprouffske, and Gary L. Westbrook. Fast NMDA Receptor-Mediated Synaptic Currents in Neurons From Mice Lacking the 2 (NR2B) Subunit. J. Neurophysiol. 83: 616-620, 2000. The N-methyl-D-aspartate (NMDA) receptor has been implicated in the formation of synaptic connections. To investigate the role of the 2 (NR2B) NMDA receptor subunit, which is prominently expressed during early development, we used neurons from mice lacking this subunit. Although 2^/ mice die soon after birth, we examined whether NMDA receptor targeting to the postsynaptic membrane was dependent on the 2 subunit by rescuing hippocampal neurons from these mice and studying them in autaptic cultures. In voltage-clamp recordings, excitatory postsynaptic currents (EPSCs) from 2^/ neurons expressed an NMDA receptor-mediated EPSC that was apparent as soon as synaptic activity developed. However, compared with wild-type neurons, NMDA receptor-mediated EPSC deactivation kinetics were much faster and were less sensitive to glycine, but were blocked by Mg²⁺ or AP5. Whole cell currents from 2^/ neurons were also more sensitive to block by low concentrations of Zn²⁺ and much less sensitive to the 2-specific antagonist ifenprodil than wild-type currents. The rapid NMDA receptor-mediated EPSC deactivation kinetics and the pharmacological profile from 2^/ neurons are consistent with the expression of 1/1 diheteromeric receptors in excitatory hippocampal neurons from mice lacking the 2 subunit. Thus 1 can substitute for the 2 subunit at synapses and 2 is not required for targeting of NMDA receptors to the postsynaptic membrane.