Enhanced odor discrimination and impaired olfactory memory by spatially controlled switch of AMPA receptors.
Genetic perturbations of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs) are widely used to dissect molecular mechanisms of sensory coding, learning, and memory. In this study, we investigated the role of Ca2+-permeable AMPARs in olfactory behavior. AMPAR modification was obtained by depletion of the GluR-B subunit or expression of unedited GluR-B(Q), both leading to increased Ca2+ permeability of AMPARs. Mice with this functional AMPAR switch, specifically in forebrain, showed enhanced olfactory discrimination and more rapid learning in a go/no-go operant conditioning task. Olfactory memory, however, was dramatically impaired. GluR-B depletion in forebrain was ectopically variable ("mosaic") among individuals and strongly correlated with decreased olfactory memory in hippocampus and cortex. Accordingly, memory was rescued by transgenic GluR-B expression restricted to piriform cortex and hippocampus, while enhanced odor discrimination was independent of both GluR-B variability and transgenic GluR-B expression. Thus, correlated differences in behavior and levels of GluR-B expression allowed a mechanistic and spatial dissection of olfactory learning, discrimination, and memory capabilities.
Shimshek
Derya R
DR
Max-Planck-Institut für medizinische Forschung, Heidelberg, Germany.
Bus
Thorsten
T
Kim
Jinhyun
J
Mihaljevic
Andre
A
Mack
Volker
V
Seeburg
Peter H
PH
Sprengel
Rolf
R
Schaefer
Andreas T
AT
D000818:Animals; D015139:Blotting, Southern; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D014644:Genetic Variation; D006579:Heterozygote; D006624:Hippocampus / Q000378:metabolism; D015151:Immunoblotting; D007858:Learning; D008568:Memory; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008954:Models, Biological; D015233:Models, Statistical; D009474:Neurons / Q000378:metabolism; D009830:Olfactory Bulb / Q000378:metabolism; D010641:Phenotype; D016548:Prosencephalon / Q000378:metabolism; D017966:Pyramidal Cells / Q000378:metabolism; D018091:Receptors, AMPA / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism; D015203:Reproducibility of Results; D012903:Smell; D009435:Synaptic Transmission; D013997:Time Factors; D019076:Transgenes
D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D002118:Calcium