Cortical AMPA receptors: age-dependent regulation by cellular depolarization and agonist stimulation.
We have recently shown that a high-affinity AMPA receptor labelled with the antagonist [3H]CNQX can be regulated in a 'living' cortical slice preparation by agonist stimulation or changes in electrical activity (Lanius, R.A. and Shaw, C. (1992) Anat. Rec., in press). Based on a study of GABAA receptors (Shaw, C. and Scarth, B.A. (1992) Mol. Brain Res., in press), which showed age-dependent changes in regulation, we have now investigated the regulation of high-affinity AMPA receptors in neocortex at different stages in postnatal development. The results show that regulation by agonist stimulation and increases in bioelectric activity are age-dependent in amount and, in the latter case, in direction. Agonist stimulation using quisqualate resulted in a significant receptor down-regulation of approximately 7% at ages less than 20 days postnatal; in adult rats quisqualate led to a significant 23% decrease. Changes in bioelectric activity induced by a combination of veratridine and glutamate showed a significant increase in AMPA receptor number of 16% at ages less than 20 days, whereas such treatment resulted in a significant 18% decrease in adult rats. The present data reveal a near mirror-image to the effects of veratridine and glutamate and agonist on GABAA receptors in the same preparation, but with a temporal mismatch in the amount and direction of regulation. We speculate that the age-dependent differences in direction of regulation for the receptor populations which serve key excitatory and inhibitory functions in cortex may provide a molecular basis for the gradual decline of neuronal plasticity during the critical period.
Shaw
C
C
Department of Ophthalmology, University of British Columbia, Vancouver, Canada.
Lanius
R A
RA
D000375:Aging / Q000502:physiology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D007608:Kainic Acid / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009118:Muscimol / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D016318:Quisqualic Acid / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid / Q000187:drug effects / Q000502:physiology*; D017981:Receptors, Neurotransmitter / Q000187:drug effects / Q000502:physiology*; D014701:Veratridine / Q000494:pharmacology
D005971:Glutamates; D018091:Receptors, AMPA; D017459:Receptors, Amino Acid; D017981:Receptors, Neurotransmitter; D009118:Muscimol; D018698:Glutamic Acid; D016202:N-Methylaspartate; D014701:Veratridine; D016318:Quisqualic Acid; D007608:Kainic Acid