Different Forms of AMPA Receptor Mediated LTP and Their Correlation to the Spatial Working Memory Formation.

Derya R Shimshek,Verena Marx,Vidar Jensen,Georg Köhr,Bettina Schupp,Rolf Sprengel,Liliana E Layer,Thorsten Bus

doi:10.3389/fnmol.2017.00214

Abstract

Spatial working memory (SWM) and the classical, tetanus-induced long-term potentiation (LTP) at hippocampal CA3/CA1 synapses are dependent on L-α-amino-3-hydroxy-5-methylisoxazole-4-propionate receptors (AMPARs) containing GluA1 subunits as demonstrated by knockout mice lacking GluA1. In GluA1 knockout mice LTP and SWM deficits could be partially recovered by transgenic re-installation of full-length GluA1 in principle forebrain neurons. Here we partially restored hippocampal LTP in GluA1-deficient mice by forebrain-specific depletion of the GluA2 gene, by the activation of a hypomorphic GluA2(Q) allele and by transgenic expression of PDZ-site truncated GFP-GluA1(TG). In none of these three mouse lines, the partial LTP recovery improved the SWM performance of GluA1-deficient mice suggesting a specific function of intact GluA1/2 receptors and the GluA1 intracellular carboxyl-terminus in SWM and its associated behavior.

Highlights

Changes in synaptic efficacy in the central nervous system are thought to underlie learning and memory
The cell-type specific modulation of amino-3-hydroxy-5-methylisoxazole-4-propionate receptor (AMPAR) was achieved by inactivating a floxed Gria2 gene, by activating a hypomorphic Gria2neo gene and by expressing a transgenic
In the three different mouse lines— Gria1−/−/2 Fb, Gria1−/−/2QFb, and Gria1−/−/Tg8.1—the remaining AMPAR levels and the ratios of Ca2+-permeable and Ca2+-impermeable AMPARs is very different in principal neurons of the hippocampus

Summary

INTRODUCTION

Changes in synaptic efficacy in the central nervous system are thought to underlie learning and memory. Despite the normal SRM of Gria1−/− mice a robust impairment in the rewarded alternation task on the elevated T-maze—the standard behavioral test for the spatial working memory (SWM) performance in rodents (Rawlins and Olton, 1982; Deacon et al, 2002)—was detected in Gria1−/− mice (Reisel et al, 2002) This SWM deficit was directly correlated to the LTP impairment, as shown by the partial restoration of SWM and LTP in Gria1−/− mice that express GFP-tagged-GluA1 in principal forebrain neurons (Mack et al, 2001; Schmitt et al, 2005). To further dissect AMPAR functions in LTP and SWM, we genetically activated AMPARs containing homomeric GluA3, heteromeric GluA2(Q)/3 or PDZ-site truncated GFP-GluA1(TG) in principal forebrain neurons of Gria1−/− mice and analyzed AMPAR subunit expression, pairing-induced and field-LTP and the SWM of the three different mouse lines

Ethical Statement

RESULTS

DISCUSSION