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Double Dissociation of Spike Timing-Dependent Potentiation and Depression by Subunit-Preferring NMDA Receptor Antagonists in Mouse Barrel Cortex

Banerjee, Abhishek and Meredith, Rhiannon M. and Rodriguez-Moreno, Antonio and Mierau, Susanna B. and Auberson, Yves and Paulsen, Ole (2009) Double Dissociation of Spike Timing-Dependent Potentiation and Depression by Subunit-Preferring NMDA Receptor Antagonists in Mouse Barrel Cortex. Cerebral Cortex, 19 (12). pp. 2959-2969. ISSN 1047-3211

Abstract

Spike timing--dependent plasticity (STDP) is a strong candidate for an N-methyl-D-aspartate (NMDA) receptor-dependent form of synaptic plasticity that could underlie the development of receptive field properties in sensory neocortices. Whilst induction of timingdependent
long-term potentiation (t-LTP) requires postsynaptic
NMDA receptors, timing-dependent long-term depression (t-LTD) requires the activation of presynaptic NMDA receptors at layer 4- to-layer 2/3 synapses in barrel cortex. Here we investigated the developmental profile of t-LTD at layer 4-to-layer 2/3 synapses of mouse barrel cortex and studied their NMDA receptor subunit dependence. Timing-dependent LTD emerged in the first postnatal week, was present during the second week and disappeared in the adult, whereas t-LTP persisted in adulthood. An antagonist at GluN2C/D subunit--containing NMDA receptors blocked t-LTD but not t-LTP. Conversely, a GluN2A subunit--preferring antagonist
blocked t-LTP but not t-LTD. The GluN2C/D subunit requirement for t-LTD appears to be synapse specific, as GluN2C/D antagonists did not block t-LTD at horizontal cross-columnar layer 2/3-to-layer 2/3 synapses, which was blocked by a GluN2B antagonist instead.
These data demonstrate an NMDA receptor subunit-dependent
double dissociation of t-LTD and t-LTP mechanisms at layer 4-tolayer 2/3 synapses, and suggest that t-LTD is mediated by distinct molecular mechanisms at different synapses on the same postsynaptic neuron.

Item Type: Article
Keywords: development; LTD; LTP; rodent; synaptic plasticity
Date Deposited: 13 Oct 2015 13:16
Last Modified: 13 Oct 2015 13:16
URI: https://oak.novartis.com/id/eprint/2998

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