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The Journal of Neuroscience, March 29, 2006, 26(13):3561-3566; doi:10.1523/JNEUROSCI.3154-05.2006

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Behavioral/Systems/Cognitive
The Different Effects on Recognition Memory of Perirhinal Kainate and NMDA Glutamate Receptor Antagonism: Implications for Underlying Plasticity Mechanisms

Gareth R. I. Barker,^1 * E. Clea Warburton,^1 * Timothy Koder,¹ Nigel P. Dolman,² Julia C. A. More,² John P. Aggleton,³ Zafar I. Bashir,¹ Yves P. Auberson,⁴ David E. Jane,² and Malcolm W. Brown¹

Medical Research Council Centre for Synaptic Plasticity, Departments of ¹Anatomy and ²Pharmacology, University of Bristol, Bristol BS8 1TD, United Kingdom, ³School of Psychology, University of Cardiff, Cardiff CF10 3YG, United Kingdom, and ⁴Novartis Institutes for Biomedical Research, CH-4002 Basel, Switzerland

Correspondence should be addressed to Prof. Malcolm W. Brown, Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, UK. Email: m.w.brown{at}bris.ac.uk

To investigate the involvement of different types of glutamate receptors in recognition memory, selective antagonists of NMDA and kainate receptors were locally infused into the perirhinal cortex of the rat temporal lobe. Such infusion of a selective kainate receptor antagonist produced an unusual pattern of recognition memory impairment: amnesia after a short (20 min) but not a long (24 h) delay. In contrast, antagonism of perirhinal NMDA glutamate receptors by locally infused AP-5 (2-amino-5-phosphonopentanoic acid) impaired recognition memory after the long but not the short delay. For both drugs, impairment was found when the drug was present during acquisition but not when it was present during retrieval. Experiments in vitro indicate that selective antagonism of NMDA receptors containing NR2A subunits blocks perirhinal long-term potentiation (LTP), whereas antagonism of NMDA receptors containing NR2B subunits blocks long-term depression (LTD). However, recognition memory after a 24 h delay was impaired only when both an NR2A and an NR2B antagonist were infused together, not when either was infused separately. These results establish that kainate receptors have a role in recognition memory that is distinct from that of NMDA receptors, that there must be at least two independent underlying memory mechanisms in the infused region, that this region and no other is necessary for both short-term and long-term familiarity discrimination, and that perirhinal-dependent long-term recognition memory does not rely solely on processes used in NMDA-dependent LTP or LTD (although it might be independently supported by components of each type of process with one substituting for the other).

Key words: familiarity discrimination; temporal lobe; LTP/LTD; plasticity; AP-5; NMDA; kainate; recognition memory; perirhinal

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Received July 29, 2005; revised Jan. 10, 2006; accepted Jan. 30, 2006.

Correspondence should be addressed to Prof. Malcolm W. Brown, Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, UK. Email: m.w.brown{at}bris.ac.uk

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