Comment on "Role of NMDA Receptor Subtypes in Governing the Direction of Hippocampal Synaptic Plasticity"

Institute of Neurology, University College LondonQueen SquareLondon WC1N 2BG, UK.
Science (Impact Factor: 33.61). 10/2004; 305(5692):1912; author reply. DOI: 10.1126/science.1101128
Source: PubMed


Activation of N-methyl-D-aspartate subtype glutamate receptors (NMDARs) is required for long-term potentiation (LTP) and long-term depression (LTD) of excitatory synaptic transmission at hippocampal CA1 synapses, the proposed cellular substrates of learning and memory. However, little is known about how activation of NMDARs leads to these two opposing forms of synaptic plasticity. Using hippocampal slice preparations, we showed that selectively blocking NMDARs that contain the NR2B subunit abolishes the induction of LTD but not LTP. In contrast, preferential inhibition of NR2A-containing NMDARs prevents the induction of LTP without affecting LTD production. These results demonstrate that distinct NMDAR subunits are critical factors that determine the polarity of synaptic plasticity.

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    • "In agreement with this, we observed a strong reduction of dendrite branching in SOD1 G93A M1 neurons in which postsynaptic expression of NR2A is decreased. Our findings therefore agree with a scenario in which an altered NR2A expression decreases dendritic branch complexity and reduces LTP at cortical synapses, as already shown in the hippocampus both in vitro (Liu et al. 2004; Massey et al. 2004) and in vivo (Fox et al. 2006). Indeed, a direct implication of CaMKIIs signaling in Ca 2+ -dependent development of dendritic arbor in cortical neurons has also been demonstrated although other members of the CaMK family might also be involved (Wayman et al. 2008). "
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    • "Besides modulating NMDA receptor function zinc also acts on other postsynaptic channels and receptors including voltage gated ion channels, GABA (γaminobutyric acid), dopamine and Trk (tyrosine kinase) receptors (Bitanihirwe and Cunningham 2009) and therefore cannot be used as a selective inhibitor for NR2A-NMDA receptors. More recent studies reported the discovery of a new NMDAR antaogonist, NVP- AAM077 ([(R)-[(S)-1-(4-bromophenyl)-ethylamino]-(2, 3-dioxo-1,2,3,4- tetrahydroquinoxalin-5-yl)-methyl]-phosphonic acid)) (Auberson et al. 2002), which was claimed to display strong selectivity for NR2A-containing NMDA receptors (Liu et al. 2004). However, its selectivity has been debated in several studies (Feng et al. 2004; Berberich et al. 2005; Weitlauf et al. 2005; Frizelle et al. 2006; Neyton and Paoletti 2006; de Marchena et al. 2008). "
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    • "It is well established that synaptic NMDAR composition influences the induction of synaptic plasticity (Barria and Malinow, 2005; Gardoni et al., 2009; Jung et al., 2008; Liu et al., 2004a; Tang et al., 1999). Yet, the spatial scales of NMDAR compositional changes and the precise role of specific receptor subunits are controversial (Barria and Malinow, 2005; Jung et al., 2008; Liu et al., 2004a; Massey et al., 2004; Morishita et al., 2007; Philpot et al., 2007; Tang et al., 1999; Zhou et al., 2007). A prevailing model suggests that the relative levels of NR2A and NR2B modify the threshold for LTP and LTD induction (Kopp et al., 2006; Philpot et al., 2007; Yashiro and Philpot, 2008). "
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