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2_test

{"project":"2_test","denotations":[{"id":"16216087-15572116-84723746","span":{"begin":540,"end":541},"obj":"15572116"},{"id":"16216087-15572116-84723747","span":{"begin":1325,"end":1326},"obj":"15572116"},{"id":"16216087-14566341-84723748","span":{"begin":1327,"end":1328},"obj":"14566341"},{"id":"T61191","span":{"begin":540,"end":541},"obj":"15572116"},{"id":"T47715","span":{"begin":1325,"end":1326},"obj":"15572116"},{"id":"T52316","span":{"begin":1327,"end":1328},"obj":"14566341"}],"text":"If the GluR-B/GluR-B(Q) switch-induced alterations in the Ca2+ permeability of the AMPA channels are linked to enhanced odor discrimination and learning, the depletion of the GluR-B subunit should lead to a similar phenotypic readout. We therefore trained nine GluR-BΔFB mice and nine littermate controls in the same automated associative go/no-go olfactory conditioning task described above. To cover even small phenotypic changes in olfaction, we tested different odor pairs, “simple” monomolecular odors and “difficult” binary mixtures [3]. After habituation, GluR-BΔFB and control mice were trained to discriminate between the “simple” monomolecular odors amylacetate and ethylbutyrate, and subsequently additionally on a “difficult” discrimination task consisting of similar binary mixtures of cineol and eugenol; and finally again on a “simple” discrimination task with the monomolecular odors pelargonic and valeric acid. Similar to GluR-BΔECS:FB, GluR-BΔFB mice also showed enhanced learning and discrimination compared with controls (Figure 2B; group effect: F(1,16) = 6.55; p \u003c 0.05). Increased discrimination performance is expected to show more pronounced effects for closely related odors because of the more challenging “difficult” discrimination task that is closer to the psychophysical limits of the system [3,4]. Consistent with this notion, differences between GluR-BΔFB and control mice were not only larger if the detailed sampling pattern and discrimination index were investigated (Figure 2C and 2D, group effect: F(1,16) = 29.5; p \u003c 10−4), but in particular for the discrimination of binary mixtures with similar composition (group effect: F(1,16) = 27.8; p \u003c 10−4 for the mixture; FAA EB(1,16) = 7.0; p = 0.02, and FPel Val(1,16) = 5.8; p = 0.03 for the “simple” discrimination tasks; 3-way ANOVA: F(6,96) = 2.9; p = 0.01). As activity, measured by the intertrial interval, was not significantly different between genotypes (F(1,16) = 3.1; p = 0.1), and analysis of the lick frequency showed a tendency to reduced motivation of GluR-BΔFB mice in this particular task (F(1,16) = 9.2; p \u003c 0.01), we conclude that depletion of GluR-B in forebrain areas indeed resulted in increased olfactory learning and discrimination performances, rather than motivational alterations. To assess olfaction specificity, we trained ten GluR-BΔFB mice and ten controls in a nonolfactory hippocampus-dependent spatial learning task (elevated Y-maze). Performance in this task was not improved compared with controls (Figure S2); on the contrary, the acquisition of this task was slightly impaired, allowing the conclusion that the enhanced olfactory discrimination performance is likely to be specific to the sense of smell and possibly related to enhanced discrimination capability, rather than a general increase in alertness. Furthermore, enhancement in odor discrimination in both GluR-BΔECS:FB and GluR-BΔFB mice makes it likely that improvement in this task results from the common AMPAR property change mediated by the depletion of GluR-B and the lack of the Q/R site-edited GluR-B subunit, both resulting in Ca2+-permeable AMPARs. Thus, this suggests that increased Ca2+ influx via AMPARs leads to enhanced olfactory learning and discrimination."}

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PMC:1255741 / 17063-20320 JSON TXT