PMC:1255741 / 43964-47637 JSONTXT

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Reduced olfactory memory can also not be simply attributed to increased extinction, as no significant trial-group interactions were observed and also, when restricted to the first unrewarded memory trials, a significant impairment was observed (Figure S3A). Additionally, investigating relearning of the first discrimination task revealed a significant correlation with the memory performance, showing a “memory” deficit under extinction-free conditions (Figure S3B). Finally, in other memory-related tasks, such as a hippocampus-dependent spatial reference memory task (Figure S2), mice with GluR-B depletion were not impaired after task acquisition. We therefore conclude that forebrain-specific ablation of GluR-B results in a specific loss of long-term olfactory memory but, at the same time, in enhanced odor discrimination and learning capabilities.\nTo dissect the discrimination, learning, and memory phenotypes, and ultimately identify potential cellular correlates, we made use of the variegated Cre expression of TgCre4 mice. Therefore, residual GluR-B levels were determined from each mouse that had been tested in the behavioral experiments, and levels were correlated with odor learning, discrimination, and olfactory memory. The significant direct correlation between residual GluR-B levels in hippocampus and cortical areas with olfactory memory suggested hippocampal and/or cortical neurons as putative mediators for odor memorization and/or storage. No measure of discrimination and learning, on the other hand, correlated with residual GluR-B levels; even the smallest reduction in GluR-B levels (about 20%–60%) was sufficient to establish and saturate enhanced odor discrimination capabilities. Together, this allows the conclusion that distinct mechanisms mediate discrimination/learning and memory. This is furthermore consistent with a prominent role of cortical areas or hippocampus in olfactory memory, although GluR-B levels in the olfactory bulb were also weakly correlated with memory performance. Transgenic expression of GFPGluR-B in piriform cortex and hippocampus indeed rescued memory to an extent strikingly consistent with the transgenic protein levels (approximately 10% of wild-type GluR-B), confirming the reliability of the correlation analysis and the sensitivity of the behavioral assay.\nIn general, the hippocampus is thought to be involved in only those olfactory memory tasks that involve temporal sequence analysis or require other higher cognitive features [2,13,72–74]. In particular, extensive lesions to the hippocampal formation in rats do not interfere with long-term olfactory memory in go/no-go successive olfactory discrimination tasks [72], such as the one described. This leaves piriform cortex as the most prominent candidate for the locus of the olfactory memory deficit described, consistent with the prevalent view of piriform cortex as an associational memory structure [75] and learning-associated changes in piriform cortex 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