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Dissecting spatial knowledge from spatial choice by hippocampal NMDA receptor deletion

Nature Neuroscience volume 15, pages 1153–1159 (2012)Cite this article

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Abstract

Hippocampal NMDA receptors (NMDARs) and NMDAR-dependent synaptic plasticity are widely considered crucial substrates of long-term spatial memory, although their precise role remains uncertain. Here we show that Grin1ΔDGCA1 mice, lacking GluN1 and hence NMDARs in all dentate gyrus and dorsal CA1 principal cells, acquired the spatial reference memory water maze task as well as controls, despite impairments on the spatial reference memory radial maze task. When we ran a spatial discrimination water maze task using two visually identical beacons, Grin1ΔDGCA1 mice were impaired at using spatial information to inhibit selecting the decoy beacon, despite knowing the platform's actual spatial location. This failure could suffice to impair radial maze performance despite spatial memory itself being normal. Thus, these hippocampal NMDARs are not essential for encoding or storing long-term, associative spatial memories. Instead, we demonstrate an important function of the hippocampus in using spatial knowledge to select between alternative responses that arise from competing or overlapping memories.

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Figure 1: Removal of NMDARs in dentate gyrus and CA1.
Figure 2: Loss of functional NMDA receptors at CA3-to-CA1 synapses in the dorsal CA1 region.
Figure 3: Associative long-term spatial reference memory in the Morris water maze.
Figure 4: Associative long-term spatial reference memory on the radial maze task.
Figure 5: Preserved visual discrimination learning in Grin1ΔDGCA1 mice.
Figure 6: Spatial memory and choice performance on the spatial-discrimination beacon water maze task.
Figure 7: Normal performance of Grin1ΔDGCA1 mice on the visual-discrimination beacon water maze task.

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Acknowledgements

We thank U. Amtmann, H. Monyer and I. Bertocchi for in situ hybridization, and W. Tang and D. Arcos Diaz for recombinant adeno-associated virus injections. We thank R. Deacon for assistance with lesion surgeries. This work was supported by a grant from the European Commission to the EUSynapse project (LSHM-CT-2005-019055) to P.H.S., Wellcome Trust Senior Research Fellowships 074385 and 087736 to D.M.B., a grant from the German Research Foundation (SFB636/A4; BMFT:NGFN/SP10, DFG-GA 427/8-1) to R.S. and a grant from the Bauer-Stiftung to T.B. Ø.H. and V.J. were supported by the Letten Foundation.

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Authors and Affiliations

  1. Department of Experimental Psychology, University of Oxford, Oxford, UK

    David M Bannerman, Amy Taylor, David J Sanderson & J Nicholas P Rawlins

  2. Max Planck Institute for Medical Research, Heidelberg, Germany

    Thorsten Bus, Inna Schwarz, Peter H Seeburg & Rolf Sprengel

  3. Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway

    Vidar Jensen & Øivind Hvalby

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Contributions

R.S. and P.H.S. delineated the genetic concept. T.B., I.S. and R.S. generated and molecularly analyzed the Grin1ΔDGCA1 mice. Ø.H. and V.J. performed the electrophysiological analysis. D.M.B. designed the behavioral experiments. D.M.B., D.J.S. and A.T. performed behavioral analyses. D.M.B., T.B., R.S., J.N.P.R. and P.H.S. wrote the manuscript.

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Correspondence to David M Bannerman or Peter H Seeburg.

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Bannerman, D., Bus, T., Taylor, A. et al. Dissecting spatial knowledge from spatial choice by hippocampal NMDA receptor deletion. Nat Neurosci 15, 1153–1159 (2012). https://doi.org/10.1038/nn.3166

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