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Reports that plasticity of mature hippocampal CA1 synapses is dependent on L-alpha-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors containing the glutamate receptor A subunit. Restoration of plasticity by controlled expression of green fluorescent protein-tagged GluR-A; Mediation of the establishment of mature hippocampal circuits.

Genetic perturbations of α-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. Genetic manipulation of AMPA receptors in mouse forebrain dissects specific contributions of AMPA receptor expression variation in piriform cortex and hippocampus to olfactory learning and memory, not discrimination. [ABSTRACT FROM AUTHOR]

Activity-driven delivery of AMPA receptors is proposed to mediate glutamatergic synaptic plasticity, both during development and learning. In hippocampal CA1 principal neurons, such trafficking is primarily mediated by the abundant GluR-A subunit. We now report a study of GluR-Blong, a C-terminal splice variant of the GluR-B subunit. GluR-Blong synaptic delivery is regulated by two forms of activity. Spontaneous synaptic activity-driven GluR-Blong transport maintains one-third of the steady-state AMPA receptor-mediated responses, while GluR-Blong delivery following the induction of LTP is responsible for approximately 50% of the resulting potentiation at the hippocampal CA3 to CA1 synapses at the time of GluR-Blong peak expression—the second postnatal week. Trafficking of GluR-Blong-containing receptors thus mediates a GluR-A-independent form of glutamatergic synaptic plasticity in the juvenile hippocampus. [Copyright &y& Elsevier]

We demonstrate the fundamental importance of glutamate receptor B (GluR-B) containing AMPA receptors in hippocampal function by analyzing mice with conditional GluR-B deficiency in postnatal forebrain principal neurons (GluR-BΔFb). These mice are as adults sufficiently robust to permit comparative cellular, physiological, and behavioral studies. GluR-B loss induced moderate long-term changes in the hippocampus of GluR-BΔFb mice. Parvalbumin-expressing interneurons in the dentate gyrus and the pyramidal cells in CA3 were decreased in number, and neurogenesis in the subgranular zone was diminished. Excitatory synaptic CA3-to-CA1 transmission was reduced, although synaptic excitability, as quantified by the lowered threshold for population spike initiation, was increased compared with control mice. These changes did not alter CA3-to-CA1 long-term potentiation (LTP), which in magnitude was similar to LTP in control mice. The altered hippocampal circuitry, however, affected spatial learning in GluR-BΔFb mice. The primary source for the observed changes is most likely the AMPA receptor-mediated Ca 2+ signaling that appears after GluR-B depletion, because we observed similar alterations in GluR-BΔFb mice in which the expression of Ca 2+-permeable AMPA receptors in principal neurons was induced by postnatal activation of a Q/R-site editing-deficient GluR-B allele. [ABSTRACT FROM AUTHOR]