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that neuronal circuits underlying odor discrimination, as well as olfactory memory, rely on properties of fast excitatory neurotransmission mediated by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors (AMPARs), we sought to alter, by genetic means, the specific functional contribution of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) channels containing the dominant subunit GluR-B. Of the four AMPAR constituents, GluR-A to D (GluR1 to 4), which form tetrameric channels with different binary subunit combinations, GluR-B is contained in the majority of AMPARs. GluR-B is critically involved in the formation and trafficking of AMPARs, and dominates their ion conductance and gating properties [40–46]. Notably, the normally low Ca2+ permeability of AMPA channels in principal neurons is solely mediated by GluR-B, due to a unique arginine residue (R587) in the functionally critical glutamine/arginine (Q/R) site of the pore-forming segment M2 [44,47,48], resulting from RNA editing of GluR-B pre-mRNA ([49]; reviewed in [50]). Hence, either GluR-B deficiency, or the expression of Q/R site-unedited GluR-B with a glutamine residue at the critical channel site, leads to increased Ca2+ permeability of AMPA channels, as amply demonstrated in gene-targeted mice [51,53,58,60]. Thus, the absence of GluR-B, or the expression of GluR-B(Q) in the olfactory bulb, may generate increased inhibition in mitral cells. Moreover, the ablation of GluR-B, but also changes in the extent of Q/R site editing of GluR-B, can alter the strength of excitatory synaptic transmission in the genetically addressed neuronal populations [51,58,60], thus potentially shifting the balance of excitatory and inhibitory transmission in the affected circuits. Similarly, changes in synaptic plasticity due to Ca2+-permeable AMPARs [51,52,60], e.g., in piriform cortex, might alter odor memorization processes. Thus, alterations of AMPAR properties in these brain regions will allow investigation and possibly separation of mechanisms underlying these behavioral traits."}

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