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This Article Full Text Full Text (PDF) All Versions of this Article: 565/2/579    most recent jphysiol.2004.081802v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Taverna, F. A. Articles by Roder, J. C. Search for Related Content PubMed PubMed Citation Articles by Taverna, F. A. Articles by Roder, J. C.

¹ Samuel Lunenfeld Research Institute, Mount Sinai Hospital, Toronto, Ontario, Canada M5G 1X5
² Department of Psychology and Neuroscience, University of Lethbridge, Lethbridge, Alberta, Canada T1K 3M4
³ Department of Physiology, Programme in Brain and Behaviour, Hospital for Sick Children, University of Toronto, Toronto, Canada M5G 1X8
⁴ Department of Biochemistry, Tohoku University, Graduate School of Medicine 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan
⁵ Department of Physiology, SUNY-Downstate, Brooklyn, NY 11203, USA
⁶ MRC Centre for Synaptic Plasticity, Bristol BS8 1TD, UK

There is growing evidence that NMDA receptor-dependent long-term potentiation (LTP) in the hippocampus mediates the synaptic plasticity that underlies spatial learning and memory. LTP deficiencies correlate well with spatial memory deficits and LTP enhancements may improve spatial memory. In addition, LTP deficiencies are associated with abnormal place cells as expected from the spatial mapping hypothesis of hippocampal function. In contrast, nothing is known on how enhanced NMDA receptor-dependent LTP affects place cells. To address this question we recorded place cells from mice lacking the nociceptin receptor (NOP₁/ORL₁/OP4) that have enhanced hippocampal LTP. We found that the enhanced LTP was mediated by NMDA receptors, did not require L-type calcium channels, and occurred only when high frequency tetanizing stimulus trains were used. Place cells in nociceptin receptor knockout mice were abnormal in several ways: they were less stable, had noisier positional firing patterns, larger firing fields and higher discharge rates inside and outside the firing fields. Our results suggest that excessive LTP can cause subnormal hippocampal place cell function. The effects of LTP enhancement on place cell function may therefore also depend on molecular details of synaptic plasticity, including the relationship between stimulus frequency and synaptic strength, and not merely on the magnitude of synaptic strength increases. The data have important clinical implications on development of strategies to improve cognitive function.

(Received 6 February 2005; accepted after revision 17 March 2005; first published online 17 March 2005)
Corresponding author F. A. Taverna: Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Avenue Toronto, Ontario, Canada M5G 1X5. Email: taverna{at}mshri.on.ca

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