Stoichiometries of AMPA receptor subunit mRNAs in rat brain fall into discrete categories

Abstract

In situ hybridization was used to estimate the relative concentrations of mRNAs encoding different subunits (GluR1-4) of alpha-amino 3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA)-type glutamate receptors in rat brain and to test the hypothesis that within-region expression profiles reflect a limited number of recurring patterns. Fractional subunit mRNA concentrations were calculated for 33 brain regions, and cluster analysis methods were applied to test for statistically meaningful groupings in the data. Four relatively homogeneous classes were identified and designated as AMPA receptor (AR) categories, numbered according to dominant subunit mRNAs. The AR-1 class (47% GluR1 mRNA) was expressed by structures near the mesodiencephalic border, including basal ganglia-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 fields as hippocampus and substantia nigra pars compacta. The AR-2,3 grouping (33% GluR2, 31% GluR3) was associated with the sensory relay and reticular thalamic nuclei. It is suggested that AR-1,2 and AR-2, the most closely related categories in clustering space, are largely telencephalic receptors with the former predominant in the subcortex and the latter in the cortex. The AR-2,3 class is associated with ascending sensory stations, whereas AR-1 appears to include several smaller categories 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 limited number of recurring types.

GABAA and α-Amino-3-hydroxy-5-methylsoxazole-4-propionate Receptors Are Differentially Affected by Aging in the Rat Hippocampus

“…As shown in Fig. 7A, the relative proportion of the different AMPA receptor subunits, from both adult and aged hippocampus, agree with that previously reported (33). As also shown, no gross changes with aging were detected.…”

Adult AMPA GLUA1 Receptor Subunit Loss in 5-HT Neurons Results in a Specific Anxiety-Phenotype with Evidence for Dysregulation of 5-HT Neuronal Activity

“…In previous work we observed that AMPA receptor-mediated synaptic responses in the hippocampal CA1 pyramidal cells of global Gria1-knockout mice are preserved indicating that, for synaptic transmission, the missing GluA subunits can be substituted by other AMPA receptor subunits (Zamanillo et al, 1999). Dense expression of both Gria2 and Gria4 subunit mRNA and low Gria3 mRNA expression have been reported previously in the ascending raphe nuclei of the midbrain (Gold et al, 1997;Sato et al, 1993). Thus, we hypothesize the enhanced AMPA response observed in 5-HT neurons lacking GLUA1 is mediated by receptors composed of the remaining subunits, which effectively substitute for GLUA1.…”

“…Gria1 mRNA has been demonstrated in most neuronal populations of the brain including the ascending raphe nuclei (Gold et al, 1997;Sato et al, 1993), but Gria1 mRNA or GLUA1 protein expression specifically in serotonergic neurons has not, as yet, been confirmed. Here we show that in control mice GLUA1 is present in the overwhelming majority of DRN and MRN neurons, which co-label for TPH2 (and hence are presumed to be 5-HT neurons).…”

Binding Characteristics of a Potent AMPA Receptor Antagonist [3H]Ro 48‐8587 in Rat Brain

“…1, 1998 (Hampson eta!., 1992;Petralia and Wenthold, 1992;Martin et a!., 1993;Baude et al, 1994;Bernard et al, 1997;Petralia et a!., 1997). These studies have revealed that in adult rat brain G1uR1-4 transcripts (mainly the flip variant) have a unique subunit-specific distribution (see Bahn and Wisden, 1997;Gold et a!., 1997). Hippocampal CAl -4 pyramidal cells and dentate gyrus granule cells express high levels of G1uR1 -3 mRNAs.…”

“…AMPA receptor subunits G1uR1 -4 are differentially regulated during ontogeny, and in adult rat brain they have only partially overlapping distributions (Keinanen et al, 1990;Monyer et a!., 1991;Hampson et al, 1992;Petralia and Wenthold, 1992;Martin et al, 1993;Sato et a!., 1993;Baude et al, 1994;Bahn and Wisden, 1997;Bernard et al, 1997;Petralia eta!., 1997). The stoichiometries of AMPA receptor subunit mRNAs in rat brain suggest the existence of four classes of receptor complexes (Gold et a!., 1997). Kainate receptor gene expression in adult rat brain (G!uR5-7 and KA-1 and -2; Bahn et a!., 1994) differs from AIvIPA receptor expression in its distribution.…”