Long-Lasting NMDA Receptor-Mediated EPSCs in Mouse Striatal Medium Spiny Neurons

Stephen M. Logan, John G. Partridge, Jose A. Matta, Andres Buonanno, Stefano Vicini


Excitatory postsynaptic currents (EPSCs) from dorsolateral medium spiny neurons (MSNs) were recorded in cortico-striatal slice preparations from postnatal day 6–8 (P6-8) and >P12 wild-type mice and mice that were lacking either the NR2A or the NR2C subunit of the N-methyl-d-aspartate (NMDA) receptor. EPSCs were elicited by stimulation of the excitatory afferents and the NMDA and non-NMDA receptor-mediated components were pharmacologically isolated. The ratio of these components decreased with development and was significantly reduced only between age-matched +/+ and NR2A −/− neurons. In many MSNs, the NMDA-EPSC decay was characterized by the presence of a slow exponential component with a time constant lasting >1 s regardless of genotype or age. In the NR2A −/−, no developmental increase in the decay time (Tw) of the NMDA-EPSCs was observed although it was almost twofold longer than in +/+ MSNs. NR1/NR2B antagonists were ineffective in reducing the slow NMDA-EPSCs at all ages. Input-output studies revealed differences in stimulation threshold sensitivity of MSNs based on stimulus location. High-threshold responders were preferentially identified with stimulation from intracortical locations that produced considerably faster NMDA-EPSCs, whereas low-threshold responders were mainly elicited with stimulation more proximal to the striatum and exhibited slower NMDA-EPSCs. A low-affinity competitive antagonist of NMDA receptors failed to alter the decay of NMDA-EPSCs elicited from either location, suggesting that glutamate spillover is not responsible for the long-lasting NMDA-EPSCs. Our data are consistent with the expression of a unique NMDA receptor complex in MSNs with very slow deactivation kinetics.

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