DEVELOPMENTAL-CHANGES IN DEPOLARIZATION-MEDIATED AMPA RECEPTOR MODIFICATIONS AND POTASSIUM-INDUCED LONG-TERM POTENTIATION

In the present study, we examined the KC1-induced increase in H-3]amin o-3-hydroxy-5-methylisoxazole-4-propionate ([H-3]AMPA) binding in tele ncephalic synaptoneurosomes and potentiation of synaptic transmission (KLTP) in hippocampal slices during development in rats. As previously reported, KC1-induced depolarization of telencephalic synaptoneurosom es resulted in a 40 +/- 5% increase in [H-3]AMPA binding to membrane f ractions in adult rats (3 months old). KC1-induced increase in [H-3]AM PA binding was reduced to 24 +/- 5% and 15 +/- 5% at postnatal days (P ND) 25-30 and PND 15-20 respectively, and was only 6 +/- 5% at PND 5-1 0. KLTP in area CA1 of hippocampus was most pronounced in adult slices (40 +/- 5%), and was reduced to 30 +/- 5% in slices prepared from PND 25-30 animals; KC1-induced LTP was absent in CA1 hippocampal slices p repared from PND 5-10 animals (3 +/- 5%). The decrease in KC1-induced changes in AMPA receptor binding in young animals was also associated with an altered capacity of the bee venom peptide, mellitin (a phospho lipase A(2) (PLA(2)) activator), to increase [H-3]AMPA binding in syna ptoneurosomes. The smaller effect of mellitin on [H-3]AMPA binding in young animals was not due to a decreased ability of this peptide to re lease [H-3]arachidonate from synaptoneurosomes. The parallel modificat ions in the extent of depolarization-induced change in AMPA receptor b inding and excitatory synaptic transmission during development further support the hypothesis that alterations in AMPA receptor properties m ay play a critical role in synaptic plasticity.