Retinoic Acid and LTP Recruit Postsynaptic AMPA Receptors Using Distinct SNARE-Dependent Mechanisms

Neuron. 2015 Apr 22;86(2):442-56. doi: 10.1016/j.neuron.2015.03.009. Epub 2015 Apr 2.


Retinoic acid (RA)-dependent homeostatic plasticity and NMDA receptor-dependent long-term potentiation (LTP), a form of Hebbian plasticity, both enhance synaptic strength by increasing the abundance of postsynaptic AMPA receptors (AMPARs). However, it is unclear whether the molecular mechanisms mediating AMPAR trafficking during homeostatic and Hebbian plasticity differ, and it is unknown how RA signaling impacts Hebbian plasticity. Here, we show that RA increases postsynaptic AMPAR abundance using an activity-dependent mechanism that requires a unique SNARE (soluble NSF-attachment protein receptor)-dependent fusion machinery different from that mediating LTP. Specifically, RA-induced AMPAR trafficking did not involve complexin, which activates SNARE complexes containing syntaxin-1 or -3, but not complexes containing syntaxin-4, whereas LTP required complexin. Moreover, RA-induced AMPAR trafficking utilized the Q-SNARE syntaxin-4, whereas LTP utilized syntaxin-3; both additionally required the Q-SNARE SNAP-47 and the R-SNARE synatobrevin-2. Finally, acute RA treatment blocked subsequent LTP expression, probably by increasing AMPAR trafficking. Thus, RA-induced homeostatic plasticity involves a novel, activity-dependent postsynaptic AMPAR-trafficking pathway mediated by a unique SNARE-dependent fusion machinery.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Drug Synergism
  • Exocytosis / physiology*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Homeostasis / physiology
  • Long-Term Potentiation / physiology*
  • Mice
  • Neuronal Plasticity / physiology
  • Organ Culture Techniques
  • Protein Transport / physiology
  • Qa-SNARE Proteins / metabolism
  • Receptors, AMPA / drug effects*
  • Receptors, AMPA / metabolism*
  • SNARE Proteins / metabolism*
  • Synapses / metabolism
  • Synaptic Potentials / physiology
  • Tretinoin / pharmacology*


  • Qa-SNARE Proteins
  • Receptors, AMPA
  • SNARE Proteins
  • syntaxin 4, human
  • Tretinoin