title: Long-term potentiation and the role of N-methyl-D-aspartate receptors.
abstract: N-methyl-D-aspartate receptors (NMDARs) are known for their role in the induction of long-term potentiation (LTP). Here we start by reviewing the early evidence for their role in LTP at CA1 synapses in the hippocampus. We then discuss more recent evidence that NMDAR dependent synaptic plasticity at these synapses can be separated into mechanistically distinct components. An initial phase of the synaptic potentiation, which is generally termed short-term potentiation (STP), decays in an activity-dependent manner and comprises two components that differ in their kinetics and NMDAR subtype dependence. The faster component involves activation of GluN2A and GluN2B subunits whereas the slower component involves activation of GluN2B and GluN2D subunits. The stable phase of potentiation, commonly referred to as LTP, requires activation of primarily triheteromeric NMDARs containing both GluN2A and GluN2B subunits. In new work, we compare STP with a rebound potentiation (RP) that is induced by NMDA application and conclude that they are different phenomena. We also report that NMDAR dependent long-term depression (NMDAR-LTD) is sensitive to a glycine site NMDAR antagonist. We conclude that NMDARs are not synonymous for either LTP or memory. Whilst important for the induction of LTP at many synapses in the CNS, not all forms of LTP require the activation of NMDARs. Furthermore, NMDARs mediate the induction of other forms of synaptic plasticity and are important for synaptic transmission. It is, therefore, not possible to equate NMDARs with LTP though they are intimately linked. This article is part of a Special Issue entitled SI: Brain and Memory.
authors.affiliation: Center for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, United Kingdom. Electronic address: A.Volianskis@bristol.ac.uk.
authors.forename: Arturas
authors.initials: A
authors.lastname: Volianskis
authors.affiliation: Center for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, United Kingdom.
authors.forename: Grace
authors.initials: G
authors.lastname: France
authors.affiliation: Department of Biomedicine, University of Aarhus, Denmark.
authors.forename: Morten S
authors.initials: MS
authors.lastname: Jensen
authors.affiliation: Center for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, United Kingdom.
authors.forename: Zuner A
authors.initials: ZA
authors.lastname: Bortolotto
authors.affiliation: Center for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, United Kingdom.
authors.forename: David E
authors.initials: DE
authors.lastname: Jane
authors.affiliation: Center for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, United Kingdom. Electronic address: G.L.Collingridge@bristol.ac.uk.
authors.forename: Graham L
authors.initials: GL
authors.lastname: Collingridge
mesh_terms: D000818:Animals; D006624:Hippocampus / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation; D008568:Memory / Q000502:physiology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D013569:Synapses / Q000502:physiology
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate
keywords: Hippocampus; Long-term depression, LTD; Long-term potentiation, LTP; N-methyl-d-aspartate receptors, NMDARs; N-methyl-d-aspartate, NMDA; Short-term potentiation, STP