Postsynaptic, not presynaptic NMDA receptors are required for spike-timing-dependent LTD induction

• Published in: Nature neuroscience Vol. 19; no. 9; pp. 1218 - 1224
• Main Authors: Carter, Brett C, Jahr, Craig E
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.09.2016
• Subjects: Animals; Axons - metabolism; Depression (Mood disorder); Excitatory Postsynaptic Potentials - physiology; Glutamate; Lasers; Long-Term Synaptic Depression - physiology; Mice, Transgenic; Microscopy; Neuronal Plasticity - physiology; Neurons; Physiological aspects; Presynaptic Terminals - metabolism; Pyramidal Cells - physiology; Rats, Sprague-Dawley; Receptors, N-Methyl-D-Aspartate - metabolism; Receptors, Presynaptic - metabolism; Risk factors; Somatosensory Cortex - physiology; Synapses - physiology; Oregon; United States > US
• ISSN: 1097-6256; 1546-1726
• DOI: 10.1038/nn.4343

Long-term depression (LTD) between cortical layer 4 spiny stellate cells and layer 2/3 pyramidal cells requires the activation of NMDA receptors (NMDARs). In young rodents, this form of LTD has been repeatedly reported to require presynaptic NMDARs for its induction. Here we show that at this synapse in the somatosensory cortex of 2- to 3-week-old rats and mice, postsynaptic, not presynaptic NMDARs are required for LTD induction. First, we find no evidence for functional NMDARs in L4 neuron axons using two-photon laser scanning microscopy and two-photon glutamate uncaging. Second, we find that genetic deletion of postsynaptic, but not presynaptic NMDARs prevents LTD induction. Finally, the pharmacology of the NMDAR requirement is consistent with a nonionic signaling mechanism.