EVIDENCE FOR MULTIPLE AMPA RECEPTOR COMPLEXES IN HIPPOCAMPAL CA1 CA2 NEURONS/

The AMPA receptor, which is involved in most fast glutamatergic transm ission in the mammalian brain and is expressed in most neurons, is mad e up of four subunits, GluR1-4. In situ hybridization, immunocytochemi stry studies, and single-cell PCR analyses show that the number and ty pe of AMPA receptor subunits expressed vary among neuronal populations and that two to four subunits usually are expressed in each neuron, N eurons that express two or more subunits theoretically could produce m ultiple pentameric receptor complexes that differ in their subunit com positions, and these complexes could be targeted to different synaptic populations. To determine whether a single neuronal population produc es multiple AMPA receptor complexes, we used a preparation of CA1/CA2 hippocampal pyramidal neurons and immunoprecipitation with subunit-spe cific antibodies to characterize the receptor complexes, The CA1/CA2 p yramidal neurons express high levels of GluR1-3 and receive multiple e xcitatory inputs, offering the possibility that distinct receptor comp lexes may be assembled ii and expressed selectively at different synap tic populations, Our results suggest the presence of two major populat ions of AM PA receptor complexes: those made up of GluR1 and GluR2 and those made up of GluR2 and GluR3. Very few complexes contained both G luR1 and GluR3, whereas similar to 8% of the total AMPA receptor compl exes was homomeric GluR1. The integrity of the receptor complex was ve rified by measuring [H-3]AMPA binding activity in the immunoprecipitat ed fractions. These results show that AMPA receptor complexes with dif ferent subunit compositions are present in CA1/CA2 pyramidal neurons a nd suggest an additional mechanism to regulate receptor expression in neurons.