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.
Highlights
Long-term potentiation (LTP) has been extensively studied with the belief that the mechanisms involved in its generation are essentially the same as those that underlie the synaptic basis of memory (Bliss and Collingridge, 1993; Bliss et al, 2014)
In the early 1980s we found that the N-methyl-D-aspartate receptor (NMDAR) is a trigger for the induction of LTP at the Schaffer collateral-commissural pathway (SCCP) in the hippocampus (Collingridge et al, 1983b) (Fig. 1A)
The relative contribution of these, and potentially other, factors is complex and varies according to the stimulus parameters employed (Davies and Collingridge, 1993). These studies have demonstrated that the complex interplay between AMPAR and GABAR EPSPs determine how and when NMDARs contribute to the synaptic response and trigger the induction of LTP
Summary
Long-term potentiation (LTP) has been extensively studied with the belief that the mechanisms involved in its generation are essentially the same as those that underlie the synaptic basis of memory (Bliss and Collingridge, 1993; Bliss et al, 2014). LTP, and its counterpart long-term depression (LTD), comprise a family of synaptic plastic processes. They are highly complex, befitting a set of mechanisms that provide nCorrespondence to: School of Physiology & Pharmacology, Dorothy Hodgkin Building, Whitson Street, Bristol, BS1 3NY, United Kingdom. As a consequence the NMDAR has become equated with LTP and learning and memory This leads to the topic of this article in which we discuss various plasticity phenomena that are related to NMDA receptor activation, posing the question: Does NMDAR1⁄4LTP1⁄4 Memory?
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