Distinct effects of AMPAR subunit depletion on spatial memory

This is the authors' abstract. We don't add key points for this paper.

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.