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The Journal of Neuroscience, September 8, 2004, 24(36):7821-7828; doi:10.1523/JNEUROSCI.1697-04.2004
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Cellular/Molecular
Differential Roles of NR2A and NR2B-Containing NMDA Receptors in Cortical Long-Term Potentiation and Long-Term Depression
Peter V. Massey,1 Benjamin E. Johnson,1 Peter R. Moult,1 Yves P. Auberson,2 Malcolm W. Brown,1 Elek Molnar,1 Graham L. Collingridge,1 andZafar I. Bashir1 1Medical Research Council Centre for Synaptic Plasticity, Department of Anatomy, University of Bristol, Bristol BS8 1TD, United Kingdom, and 2Novartis Pharma AG, CH-4002 Basel, Switzerland
It is widely believed that long-term depression (LTD) and its counterpart, long-term potentiation (LTP), involve mechanisms that are crucial for learning and memory. However, LTD is difficult to induce in adult cortex for reasons that are not known. Here we show that LTD can be readily induced in adult cortex by the activation of NMDA receptors (NMDARs), after inhibition of glutamate uptake. Interestingly there is no need to activate synaptic NMDARs to induce this LTD, suggesting that LTD is triggered primarily by extrasynaptic NMDA receptors. We also find that de novo LTD requires the activation of NR2B-containing NMDAR, whereas LTP requires activation of NR2A-containing NMDARs. Surprisingly another form of LTD, depotentiation, requires activation of NR2A-containing NMDARs. Therefore, NMDARs with different synaptic locations and subunit compositions are involved in various forms of synaptic plasticity in adult cortex.
Key words: LTD; LTP; NR2B; NR2A; NMDARs; depotentiation
Received May 4, 2004; revised July 16, 2004; accepted July 21, 2004.
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Astrocyte control of synaptic transmission and neurovascular coupling.
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