Synapse-specific control of experience-dependent plasticity by presynaptic NMDA receptors

Neuron. 2014 Aug 20;83(4):879-93. doi: 10.1016/j.neuron.2014.07.039.


Sensory experience orchestrates the development of cortical circuitry by adaptively modifying neurotransmission and synaptic connectivity. However, the mechanisms underlying these experience-dependent modifications remain elusive. Here we demonstrate that visual experience suppresses a presynaptic NMDA receptor (preNMDAR)-mediated form of timing-dependent long-term depression (tLTD) at visual cortex layer (L) 4-2/3 synapses. This tLTD can be maintained during development, or reinstated in adulthood, by sensory deprivation. The changes in tLTD are mirrored by changes in glutamate release; visual deprivation enhances both tLTD and glutamate release. These effects require the GluN3A NMDAR subunit, the levels of which are increased by visual deprivation. Further, by coupling the pathway-specific optogenetic induction of tLTD with cell-type-specific NMDAR deletion, we find that visual experience modifies preNMDAR-mediated plasticity specifically at L4-L2/3 synapses.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Glutamic Acid / metabolism
  • Long-Term Synaptic Depression / physiology
  • Mice
  • Neuronal Plasticity / physiology*
  • Optogenetics
  • Photic Stimulation
  • Receptors, N-Methyl-D-Aspartate / genetics
  • Receptors, N-Methyl-D-Aspartate / physiology*
  • Receptors, Presynaptic / physiology*
  • Sensory Deprivation / physiology
  • Synapses / physiology*
  • Visual Cortex / metabolism
  • Visual Cortex / physiology
  • Visual Perception / physiology


  • GluN3A protein, mouse
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Presynaptic
  • Glutamic Acid