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

Abstract

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.

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Figure 1: 2PLU of MNI-glutamate and calcium influx in L4 neuronal axonal varicosities and dendritic spines.
Figure 2: Counting voltage gated calcium channels in axonal varicosities from an L4 neuron.
Figure 3: t-LTD of L4–L2/3 synapses.
Figure 4: Pharmacology of t-LTD.
Figure 5: Postsynaptic NMDARs are required for t-LTD.
Figure 6: Presynaptic NMDARs are not required for t-LTD.

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Acknowledgements

We thank D. Chiu and W. Sun for discussions and comments on the manuscript. This work was supported by US National Institutes of Health grant NS066037 (C.E.J.).

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B.C.C. and C.E.J. designed the experiments and wrote the manuscript. B.C.C. conducted and analyzed the experiments.

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Correspondence to Craig E Jahr.

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Carter, B., Jahr, C. Postsynaptic, not presynaptic NMDA receptors are required for spike-timing-dependent LTD induction. Nat Neurosci 19, 1218–1224 (2016). https://doi.org/10.1038/nn.4343

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