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AMPA receptors play a critical role in synaptic plasticity and brain development. Here we show that Ca²⁺ uptake in response to AMPA receptor activation decreases dramatically during maturation in chicken brain microslices without a change in tissue AMPA receptor content. We found that during maturation the relative concentration of GluR2 subunits increased, the concentration of the AMPA receptor-associated scaffold proteins SAP97 and GRIP decreased and that depolarization increased GluR1 phosphorylation at Ser831 in subcellular fractions enriched in postsynaptic densities at 2 weeks but not at 10 weeks. These changes are all consistent with a decreased Ca²⁺ entry through AMPA receptor channels in response to receptor activation and may account for the changes in the functional properties of the receptor, which are thought to underlie, at least in part, the physiological changes that occur with maturation.

We have shown that the synapse maturation phase of synaptogenesis is a model for synaptic plasticity that can be particularly well-studied in chicken forebrain because for most forebrain synapses, the maturation changes occur slowly and are temporally well-separated from the synapse formation phase. We have used the synapse maturation phase of neuronal development in chicken forebrain to investigate the possible link between changes in the morphology and biochemical composition of the postsynaptic density (PSD) and the functional properties of glutamate receptors overlying the PSD. Morphometric studies of PSDs in forebrains and superior cervical ganglia of chickens and rats have shown that the morphological features of synapse maturation are characteristic of a synaptic type, but that the rate at which these changes occur can vary between types of synapses within one animal and between synapses of the same type in different species. We have investigated, during maturation in the chicken forebrain, the properties of the N-methyl-D-aspartate (NMDA) subtype of the glutamate receptors, which are concentrated in the junctional membranes overlying thick PSDs in the adult. There was no change in the number of NMDA receptors during maturation, but there was an increase in the rate of NMDA-stimulated uptake of 45Ca2+ into brain prisms. This functional change was not seen with the other ionotropic subtypes of the glutamate receptor and was NMDA receptor-mediated. The functional change also correlated with the increase in thickness of the PSD during maturation that has previously been shown to be due to an increase in the amount of PSD associated Ca(2+)-calmodulin stimulated protein kinase II (CaM-PK II). Our results provide strong circumstantial evidence for the regulation of NMDA receptors by the PSD and implicate changing local concentrations of CaM-PK II in this process. The results also indicate some of the ways in which properties of existing synapses can be modified by changes at the molecular level.

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