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-mediated synaptic transmission in essentially every brain region that has been examined. In contrast, we have found that in the rat striatum, NMDA receptor-mediated current develops later in the medium-sized neurons (MSNs) than currents mediated by activation of non-NMDA receptors. MSNs were identified using infrared video microscopy, and voltage-clamped in a slice preparation using the whole-cell patch-clamp technique. Intrastriatal stimulation was used to evoke excitatory synaptic currents from slices in animals ranging in age from postnatal day (PND) 5 to 60. Though most cells from animals younger than PND 10 failed to respond to synaptic stimulation, postsynaptic responses were occasionally evoked in cells as young as PND 5. Synaptic currents from cells between PNDs 5 and 7 had a significant contribution due to activation 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 receptors increased approximately twofold from the first to the third postnatal week; no further change was observed through PND 60. At the same ages that the NMDA receptors contributed maximally to the synaptic current, the decay time constant of the NMDA receptor-mediated current decreased significantly. The increasing weight of NMDA receptor-mediated current may reflect a change in the number of functional receptors at the synapse since there was no apparent change in the voltage dependence of the current. To more completely examine receptor function early in postnatal development, NMDA and kainate were applied either iontophoretically or in the bath. Iontophoretic application of NMDA onto cells obtained from rats between PNDs 3 and 5 only occasionally evoked current, provided that the membrane was held at depolarized potentials to remove the Mg(2+) block. In contrast, application of kainate consistently evoked a response from cells of the same age group. Bath application of the same agonists provided similar results. Taken together, the present experiments demonstrate that striatal non-NMDA receptor-mediated currents are more mature than NMDA receptor-mediated currents early in development.
Hurst
R S
RS
Mental Retardation Research Center, University of California at Los Angeles, Los Angeles, Calif. 90095-1759, USA.
Cepeda
C
C
Shumate
L W
LW
Levine
M S
MS
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D003342:Corpus Striatum / Q000166:cytology* / Q000254:growth & development*; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D018756:GABA Antagonists / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009924:Organ Culture Techniques; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000502:physiology; D018092:Kainic Acid Receptors / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D015763:2-Amino-5-phosphonovalerate; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D001640:Bicuculline; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018756:GABA Antagonists; D007608:Kainic Acid; D016202:N-Methylaspartate; D018091:Receptors, AMPA; D018092:Kainic Acid Receptors; D016194:Receptors, N-Methyl-D-Aspartate