STOICHIOMETRIES OF AMPA RECEPTOR SUBUNIT MESSENGER-RNAS IN RAT-BRAIN FALL INTO DISCRETE CATEGORIES

In situ hybridization was used to estimate the relative concentrations of mRNAs encoding different subunits (GluR1-4) of alpha-amino 3-hydro xy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors in r at brain and to test the hypothesis that within-region expression prof iles reflect a limited number of recurring patterns. Fractional subuni t mRNA concentrations were calculated for 33 brain regions, and cluste r analysis methods were applied to test for statistically meaningful g roupings in the data. Four relatively homogeneous classes were identif ied and designated as AMPA receptor (AR) categories, numbered accordin g to dominant subunit mRNAs. The AR-1 class (47% GluR1 mRNA) was expre ssed by structures near the mesodiencephalic border, including basal g anglia-related areas. The AR-2 class (57% GluR2 mRNA) was expressed in cortex and tectum. The AR-1,2 class (31% GluR1, 45% GluR2) was found in the largest number of regions, including such dissimilar cell field s as hippocampus and substantia nigra pars compacta. The AR-2,3 groupi ng (33% GluR2, 31% GluR3) was associated with the sensory relay and re ticular thalamic nuclei. It is suggested that AR-1,2 and AR-2, the mos t closely related categories in clustering space, are largely telencep halic receptors with the former predominant in the subcortex and the l atter in the cortex. The AR-2,3 class is associated with ascending sen sory stations, whereas AR-1 appears to include several smaller categor ies expressed by specialized systems. If the balance of subunit mRNAs is reflected at the protein level, then the present data suggest that forebrain AMPA-type glutamate receptors can be classified into a limit ed number of recurring types. (C) 1997 Wiley-Liss, Inc.