The NMDA receptor as a target for cognitive enhancemant

Graham L Collingridge, Arturas Volianskis, Neil J Bannister, Grace M France, Lydia Hanna, Marion S Mercier, Patrick J Tidball, Guang Y Fang, Mark W Irvine, BM Costa, DT Monaghan, Zuner A Bortolotto, Elek Molnar, David Lodge, David E Jane

Research output: Contribution to journalArticle (Academic Journal)

146 Citations (Scopus)

Abstract

NMDA receptors (NMDARs) play an important role in neural plasticity including long-term potentiation and long-term depression, which are likely to explain their importance for learning and memory. Cognitive decline is a major problem facing an ageing human population, so much so that its reversal has become an important goal for scientific research and pharmaceutical development. Enhancement of NMDAR function is a core strategy toward this goal. In this review we indicate some of the major ways of potentiating NMDAR function by both direct and indirect modulation. There is good evidence that both positive and negative modulation can enhance function suggesting that a subtle approach correcting imbalances in particular clinical situations will be required. Excessive activation and the resultant deleterious effects will need to be carefully avoided. Finally we describe some novel positive allosteric modulators of NMDARs, with some subunit selectivity, and show initial evidence of their ability to affect NMDAR mediated events. This article is part of a Special Issue entitled 'Cognitive Enhancers'.
Original languageEnglish
Pages (from-to)13-26
Number of pages14
JournalNeuropharmacology
Volume64
Early online date11 Jul 2012
DOIs
Publication statusPublished - Jan 2013

Bibliographical note

Special Issue: 22nd Neuropharmacology Conference: Cognitive Enhancers

Keywords

  • synaptic plasticity, NMDA receptor, cognitive enhancement, LTP, synaptic transmission
  • hippocampus, positive allosteric modulators

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    Collingridge, G. L., Volianskis, A., Bannister, N. J., France, G. M., Hanna, L., Mercier, M. S., Tidball, P. J., Fang, G. Y., Irvine, M. W., Costa, BM., Monaghan, DT., Bortolotto, Z. A., Molnar, E., Lodge, D., & Jane, D. E. (2013). The NMDA receptor as a target for cognitive enhancemant. Neuropharmacology, 64, 13-26. https://doi.org/10.1016/j.neuropharm.2012.06.051