Neuron
Volume 84, Issue 5, 3 December 2014, Pages 1009-1022
Journal home page for Neuron

Article
Essential Role of Presynaptic NMDA Receptors in Activity-Dependent BDNF Secretion and Corticostriatal LTP

https://doi.org/10.1016/j.neuron.2014.10.045Get rights and content
Under an Elsevier user license
open archive

Highlights

  • TBS can induce NMDAR- and BDNF-dependent LTP at corticostriatal synapses

  • TBS-induced corticostriatal LTP requires actions of presynaptic NMDAR and BDNF

  • Presynaptic NMDAR is responsible for sustained axonal Ca2+ elevation by TBS

  • TBS-triggered axonal BDNF secretion requires activation of presynaptic NMDARs

Summary

Activation of N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) in postsynaptic dendrites is required for long-term potentiation (LTP) of many excitatory synapses, but the role of presynaptic axonal NMDARs in synaptic plasticity remains to be clarified. Here we report that axonal NMDARs play an essential role in LTP induction at mouse corticostriatal synapses by triggering activity-induced presynaptic secretion of brain-derived neurotrophic factor (BDNF). Genetic depletion of either BDNF or the NMDAR subunit GluN1 specifically in cortical axons abolished corticostriatal LTP in response to theta burst stimulation (TBS). Furthermore, functional axonal NMDARs were required for TBS-triggered prolonged axonal Ca2+ elevation and BDNF secretion, supporting the notion that activation of axonal NMDARs induces BDNF secretion via enhancing Ca2+ signals in the presynaptic nerve terminals. These results demonstrate that presynaptic NMDARs are equally important as postsynaptic NMDARs in LTP induction of corticostriatal synapses due to their role in mediating activity-induced presynaptic BDNF secretion.

Cited by (0)