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Hippocampal synaptic plasticity, spatial memory and anxiety

Nature Reviews Neuroscience volume 15, pages 181–192 (2014)Cite this article

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Abstract

Recent studies using transgenic mice lacking NMDA receptors in the hippocampus challenge the long-standing hypothesis that hippocampal long-term potentiation-like mechanisms underlie the encoding and storage of associative long-term spatial memories. However, it may not be the synaptic plasticity-dependent memory hypothesis that is wrong; instead, it may be the role of the hippocampus that needs to be re-examined. We present an account of hippocampal function that explains its role in both memory and anxiety.

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Figure 1: GluA1 is required for short-term, but not long-term spatial memory.
Figure 2: Impaired spatial reference memory on the radial maze but normal spatial reference memory in the open-field water maze in Grin1ΔDGCA1 mice.
Figure 3: Impaired spatial discrimination but normal non-spatial discrimination in the water maze in the Grin1ΔDGCA1 mice.
Figure 4: Distinct contributions of the dorsal and ventral hippocampus to behaviour.

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Acknowledgements

This work was supported by the Wellcome trust (grants 074385 and 087736 to D.M.B.), the European Research Council (GABAcellsAndMemory grant 250047 to H.M.), the Deutsche Forschungsgemeinschaft (SFB 636/A4 to R.S.) and the Max Planck Society (to R.S. and P.H.S.).

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Authors and Affiliations

  1. Department of Experimental Psychology, University of Oxford, Oxford, OX1 3UD, UK

    David M. Bannerman, Stephen B. McHugh & J. Nicholas P. Rawlins

  2. Max Planck Institute for Medical Research, Heidelberg, D-69120, Germany

    Rolf Sprengel & Peter H. Seeburg

  3. Department of Psychology, Durham University, Durham, DH1 3LE, UK

    David J. Sanderson

  4. Department of Clinical Neurobiology, Medical Faculty of Heidelberg University and German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany

    Hannah Monyer

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  1. David M. Bannerman
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  2. Rolf Sprengel
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  3. David J. Sanderson
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  4. Stephen B. McHugh
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  5. J. Nicholas P. Rawlins
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  6. Hannah Monyer
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Correspondence to David M. Bannerman or Peter H. Seeburg.

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Glossary

AP5

(2-amino-5-phosphopentanoate). A competitive antagonist of the NMDA-type glutamate receptor. The drug competes with glutamate to bind to the NMDA receptor and thus reduces the activity of these receptors.

Boundary vector cells

The firing of these cells depends solely on the animal's location relative to environmental boundaries and is independent of the animal's heading direction.

Dissociations

A term to describe when an experimental manipulation (for example, a lesion, genetic modification or drug treatment) affects performance on one behavioural task but not another. This is taken to suggest that different neural substrates may underlie the two behaviours.

Double dissociation

A term to describe when a given experimental manipulation affects task A but not task B, whereas a second manipulation affects task B but does not affect task A. A double dissociation is evidence that these behaviours must be supported by different neural substrates.

Grid cells

Cells that have been found in layer 2/3 of the medial entorhinal cortex and that fire at several regularly spaced locations (unlike hippocampal place cells, which fire only in one part of a given environment), with marked inhibition of firing outside these locations.

Head direction cells

Cells that are sensitive to the orientation of the animal's head with respect to the environmental frame, irrespective of the animal's spatial location within that environment. They signal a single preferred head direction, irrespective of body-orientation or current position; whether the animal is moving or stationary.

Place cells

Cells that selectively increase their firing rate only when the animal occupies a well-defined, small patch of the environment (the place field), and they rarely fire outside this region. Place cells are usually recorded in the hippocampus proper, but they are also present in other areas of the hippocampal formation (for example, the entorhinal cortex, subiculum, presubiculum and parasubiculum).

Spatial reference memory

(SRM).The ability to learn a consistent, fixed response to a spatial stimulus, reflecting a constant association between that spatial location and an outcome. For example, an animal will need to learn the spatial location of its home burrow or a reliable water source that is constant within the environment.

Spatial working memory

(SWM). The ability to maintain trial-specific information for a limited period of time so that spatial responses can be made in a flexible manner from trial to trial. This is the basis of foraging behaviour (for example, remembering where you have just been so that you can adopt an efficient search strategy).

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Bannerman, D., Sprengel, R., Sanderson, D. et al. Hippocampal synaptic plasticity, spatial memory and anxiety. Nat Rev Neurosci 15, 181–192 (2014). https://doi.org/10.1038/nrn3677

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