F.F. and V.M. contributed equally to this work.
Circuit mechanisms of GluA1-dependent spatial working memory
Article first published online: 10 SEP 2013
Copyright © 2013 Wiley Periodicals, Inc.
Volume 23, Issue 12, pages 1359–1366, December 2013
How to Cite
Freudenberg, F., Marx, V., Seeburg, P. H., Sprengel, R. and Celikel, T. (2013), Circuit mechanisms of GluA1-dependent spatial working memory. Hippocampus, 23: 1359–1366. doi: 10.1002/hipo.22184
- Issue published online: 20 NOV 2013
- Article first published online: 10 SEP 2013
- Accepted manuscript online: 8 AUG 2013 08:38AM EST
- Manuscript Accepted: 29 JUL 2013
- University of Heidelberg. Grant Number: University Grant GC791
- EUSynapse project. Grant Number: LSHM-CT-2005-019055
- Alexander von Humboldt foundation, Volkswagen foundation: Dynamik und Adaptivität neuronaler Systeme and the European Commission, Whitehall Foundation, Sloan Foundation
- spatial working memory;
- neural circuits;
- gene targeting
Spatial working memory (SWM), the ability to process and manipulate spatial information over a relatively short period of time, requires an intact hippocampus, but also involves other forebrain nuclei in both in rodents and humans. Previous studies in mice showed that the molecular mechanism of SWM includes activation of AMPA receptors containing the GluA1 subunit (encoded by gria1) as GluA1 deletion in the whole brain (gria1–/–) results in strong SWM deficit. However, since these mice globally lack GluA1, the circuit mechanisms of GluA1 contribution to SWM remain unknown. In this study, by targeted expression of GluA1 containing AMPA receptors in the forebrain of gria1–/– mice or by removing GluA1 selectively from hippocampus of mice with “floxed” GluA1 alleles (gria1fl/fl), we show that SWM requires GluA1 action in cortical circuits but is only partially dependent on GluA1-containing AMPA receptors in hippocampus. We further show that hippocampal GluA1 contribution to SWM is temporally restricted and becomes prominent at longer retention intervals (≥30 s). These findings provide a novel insight into the neural circuits required for SWM processing and argue that AMPA mediated signaling across forebrain and hippocampus differentially contribute to encoding of SWM. © 2013 Wiley Periodicals, Inc.