Delayed postnatal development of NMDA receptor function in medium-sized neurons of the rat striatum

During early postnatal development, the N-methyl-D-aspartate (NMDA) subtype of glutamate receptor plays a dominant role in excitatory amino acid-media ted synaptic transmission in essentially every brain region that has been e xamined. In contrast, we have found that in the rat striatum, NMDA receptor -mediated current develops later in the medium-sized neurons (MSNs) than cu rrents mediated by activation of non-NMDA receptors. MSNs were identified u sing infrared video microscopy, and voltage-clamped in a slice preparation using the whole-cell patch-clamp technique. Intrastriatal stimulation was u sed to evoke excitatory synaptic currents from slices in animals ranging in age from postnatal day (PND) 5 to 60. Though most cells from animals young er than PND 10 failed to respond to synaptic stimulation, postsynaptic resp onses were occasionally evoked in cells as young as PND 5. Synaptic current s from cells between PNDs 5 and 7 had a significant contribution due to act ivation of non-NMDA receptors, as evidenced by sensitivity to the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and rapidly rising and falling response components. The relative contribution of NMDA recepto rs increased approximately twofold from the first to the third postnatal we ek; no further change was observed through PND 60. At the same ages that th e NMDA receptors contributed maximally to the synaptic current, the decay t ime constant of the NMDA receptor-mediated current decreased significantly. The increasing weight of NMDA receptor-mediated current may reflect a chan ge in the number of functional receptors at the synapse since there was no apparent change in the voltage dependence of the current. To more completel y examine receptor function early in postnatal development, NMDA and kainat e were applied either iontophoretically or in the bath. Iontophoretic appli cation of NMDA onto cells obtained from rats between PNDs 3 and 5 only occa sionally evoked current, provided that the membrane was held at depolarized potentials to remove the Mg2+ block. In contrast, application of kainate c onsistently evoked a response from cells of the same age group. Bath applic ation of the same agonists provided similar results. Taken together, the pr esent experiments demonstrate that striatal non-NMDA receptor-mediated curr ents are more mature than NMDA receptor-mediated currents early in developm ent. Copyright (C) 2001 S. Karger AG, Basel.