Nature 378, 182 - 186 (09 November 1995); doi:10.1038/378182a0

Distinct components of spatial learning revealed by prior training and NMDA receptor blockade

D. M. Bannerman^*, M. A. Good^*, S. P. Butcher^†, M. Ramsay & R. G. M. Morris^‡

Centre for Neuroscience and Department of Pharmacology, University of Edinburgh Medical School, Crichton Street, Edinburgh EH8 9LE, UK
^† Fujisawa Institute for Neuroscience, University of Edinburgh, Edinburgh EH8 9JZ, UK
^* Present addresses: Department of Experimental Psychology, University of Oxford, Oxford 0X1 3UD, UK (D.M.B.); School of Psychology, Cardiff University of Wales, Cardiff CF1 3YG, UK (M.A.G.).
^‡ To whom correspondence should be addressed.

SYNAPTIC plasticity dependent on N-methyl-D-aspartate (NMDA) receptors is thought to underlie certain types of learning and memory^1–3. In support of this, both hippocampal long-term potentiation and spatial learning in a watermaze are impaired by blocking NMDA receptors with a selective antagonist D(-)-2-amino-5-phosphonovaleric acid (AP5)⁴ or by a mutation in one of the receptor subunits5. Here we report, however, that the AP5-induced learning deficit can be almost completely prevented if rats are pretrained in a different watermaze before administration of the drug. This is not because of stimulus generalization, and occurs despite learning of the second task remaining hippocampus dependent. An A PS5-induced learning deficit is, however, still seen if the animals are pretrained using a non-spatial task. Thus, despite its procedural simplicity, the watermaze may involve multiple cognitive processes with distinct pharmacological properties; although required for some component of spatial learning, NMDA receptors may not be required for encoding the spatial representation of a specific environment.

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