GLYCINE-INDUCED LONG-TERM POTENTIATION IS ASSOCIATED WITH STRUCTURAL AND FUNCTIONAL MODIFICATIONS OF PHA-AMINO-3-HYDROXYL-5-METHYL-4-ISOXAZOLEPROPIONIC ACID RECEPTORS

Global long-term potentiation (LTP) was induced in organotypic hippoca mpal slice cultures by a brief application of 10 mM glycine, Glycine-i nduced LTP was occluded by previous theta burst stimulation-induced po tentiation, indicating that both phenomena share similar cellular proc esses. Glycine-induced LTP was associated with increased [H-3] pha-ami no-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) binding in mem brane fractions as well as increased amount of a selective spectrin br eakdown product generated by calpain-mediated spectrin proteolysis, An tibodies against the C-terminal (C-Ab) and N-terminal (N-Ab) domains o f GluR1 subunits were used to evaluate structural changes in AMPA rece ptor properties resulting from glycine-induced LTP, No quantitative or qualitative changes were observed in Western blots from membrane frac tions prepared from glycine-treated slices with C-Ab, In contrast, Wes tern blots stained with N-Ab revealed the formation of a 98-kDa specie s of GluR1 subunits as well as an increased amount of immunoreactivity after glycine-induced LTP, The amount of spectrin breakdown product w as positively correlated with the amount of the 98-kDa species of GluR 1 after glycine treatment, Functional modifications of AMPA receptors were evaluated by determining changes in the effect of pressure-applie d AMPA on synaptic responses before and after glycine-induced LTP. Gly cine treatment produced a significant increase in AMPA receptor functi on after potentiation that correlated with the degree of potentiation, The results indicate that LTP induction produces calpain activation, truncation of the C-Ab domain of GluR1 subunits of AMPA receptors, and increased AMPA receptor function. They also suggest that insertion of new receptors takes place after LTP induction.