To ascertain if enhanced olfactory learning and odor discrimination may indeed correlate with the increased Ca2+ permeability of AMPA channels in the Q/R site-unedited form, we next analyzed GluR-BΔFB mice, which lack GluR-B in forebrain. This specific ablation was generated by forebrain-selective TgCre4 expression ([59] “Camkcre4”) in gene-targeted GluR-B2lox mice carrying, in both GluR-B alleles, a floxed exon 11 (Figure 2A). The specific GluR-B depletion in GluR-BΔFB mice can be monitored by immunohistochemistry (see below) and immunoblotting. In quantitative immunoblot analyses, we found GluR-B levels reduced to 28 ± 7%, 29 ± 8%, and 52 ± 9% (± SEM; n = 10) in the hippocampus, cortical areas, and olfactory bulb, respectively, relative to GluR-B levels in GluR-B2lox littermate controls. In the absence of GluR-B, the electrophysiological properties of AMPA channels become similar to those with GluR-B/GluR-B(Q) switch [51] showing strong rectification and increased Ca2+ permeability through AMPA channels (unpublished data). However, GluR-B depletion is not lethal and does not produce seizures. In addition, in contrast to the complete GluR-B knockouts, mice with forebrain-specific GluR-B depletion appeared normal throughout life with no developmental abnormalities, or difference in body size and weight in adulthood (wild-type: 31.0 g ± 1.2; GluR-BΔFB: 28.4 ± 0.9; each n = 10). Exploratory activity in an open field task was slightly increased in GluR-BΔFB mice (3,480 cm ± 180, n = 11), compared with wild-type littermates (2,512 cm ± 96, n = 12, p <0.01). Motor coordination measured in an accelerating rotarod was somewhat impaired in the mutant mice (wild-type: 156 s ± 37, n = 6; GluR-BΔFB: 37 s ± 10, n = 6; p < 0.05). Tests in the dark/light box revealed increased anxiety of GluR-BΔFB mice (latency of first exit: wild-type [17 s ± 3], GluR-BΔFB [97 s ± 42], p = 0.047; compartment changes: wild-type [17 s ± 3], GluR-BΔFB [7 ± 2], p < 0.05; time spent in lit compartment: wild-type [103 s ± 10], GluR-BΔFB [59 s ± 19], p = 0.051; each n = 6). Hence, unlike the complete GluR-B knockouts, GluR-BΔFB mice show only very minor changes in general activity and no sign of any major developmental disturbance, thus allowing detailed, quantitative behavioral investigations.