Double Dissociation of Spike Timing--.pdf

Cerebral Cortex December 2009;19:2959--2969 doi:10.1093/cercor/bhp067 Advance Access publication April 10, 2009 Double Dissociation of Spike Timing-- Dependent Potentiation and Depression by Subunit-Preferring NMDA Receptor Antagonists in Mouse Barrel Cortex Abhishek Banerjee1, Rhiannon M. Meredith1,4, Antonio Rodr??guez-Moreno1,2, Susanna B. Mierau1, Yves P. Auberson3 and Ole Paulsen1 1The Neuronal Oscillations Group, Department of Physiology, Anatomy and Genetics, Oxford, OX1 3PT, UK, 2Department of Physiology, Anatomy and Cellular Biology, University Pablo de Olavide, 41013 Seville, Spain and 3Novartis Institutes for BioMedical Research, CH-4057 Basel, Switzerland 4Current address: Department of Integrative Neurophysiology, Center for Neurogenomics and Cognitive Research (CNCR), VU University Amsterdam, the Netherlands Abhishek Banerjee and Rhiannon M. Meredith contributed equally to this work 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 timing- dependent 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