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Distinct effects of AMPAR subunit depletion on spatial memory

Pharmacological studies established a role for AMPARs in the mammalian forebrain in spatial memory performance. Here we generated global GluA1/3 double knockout mice (Gria1/3(−/−)) and conditional knockouts lacking GluA1 and GluA3 AMPAR subunits specifically from principal cells across the forebrain...

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Detalles Bibliográficos
Autores principales: Eltokhi, Ahmed, Bertocchi, Ilaria, Rozov, Andrei, Jensen, Vidar, Borchardt, Thilo, Taylor, Amy, Proenca, Catia C., Rawlins, John Nick P., Bannerman, David M., Sprengel, Rolf
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10590979/
https://www.ncbi.nlm.nih.gov/pubmed/37876813
http://dx.doi.org/10.1016/j.isci.2023.108116
Descripción
Sumario:Pharmacological studies established a role for AMPARs in the mammalian forebrain in spatial memory performance. Here we generated global GluA1/3 double knockout mice (Gria1/3(−/−)) and conditional knockouts lacking GluA1 and GluA3 AMPAR subunits specifically from principal cells across the forebrain (Gria1/3(ΔFb)). In both models, loss of GluA1 and GluA3 resulted in reduced hippocampal GluA2 and increased levels of the NMDAR subunit GluN2A. Electrically-evoked AMPAR-mediated EPSPs were greatly diminished, and there was an absence of tetanus-induced LTP. Gria1/3(−/−) mice showed premature mortality. Gria1/3(ΔFb) mice were viable, and their memory performance could be analyzed. In the Morris water maze (MWM), Gria1/3(ΔFb) mice showed profound long-term memory deficits, in marked contrast to the normal MWM learning previously seen in single Gria1(−/−) and Gria3(−/−) knockout mice. Our results suggest a redundancy of function within the pool of available ionotropic glutamate receptors for long-term spatial memory performance.