Cortical Synaptic AMPA Receptor Plasticity during Motor Learning

Neuron. 2020 Mar 4;105(5):895-908.e5. doi: 10.1016/j.neuron.2019.12.005. Epub 2019 Dec 31.


Modulation of synaptic strength through trafficking of AMPA receptors (AMPARs) is a fundamental mechanism underlying synaptic plasticity, learning, and memory. However, the dynamics of AMPAR trafficking in vivo and its correlation with learning have not been resolved. Here, we used in vivo two-photon microscopy to visualize surface AMPARs in mouse cortex during the acquisition of a forelimb reaching task. Daily training leads to an increase in AMPAR levels at a subset of spatially clustered dendritic spines in the motor cortex. Surprisingly, we also observed increases in spine AMPAR levels in the visual cortex. There, synaptic potentiation depends on the availability of visual input during motor training, and optogenetic inhibition of visual cortex activity impairs task performance. These results indicate that motor learning induces widespread cortical synaptic potentiation by increasing the net trafficking of AMPARs into spines, including in non-motor brain regions.

Keywords: AMPA receptors; long-term potentiation; motor cortex; motor learning; synaptic clustering; synaptic plasticity; two-photon imaging; visual cortex.

Publication types

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

MeSH terms

  • Animals
  • Dendritic Spines / metabolism*
  • Forelimb
  • Intravital Microscopy
  • Learning*
  • Mice
  • Microscopy, Fluorescence
  • Motor Activity*
  • Motor Cortex / metabolism*
  • Neuronal Plasticity*
  • Neurons / metabolism*
  • Optogenetics
  • Protein Transport
  • Psychomotor Performance
  • Receptors, AMPA / metabolism*
  • Spatio-Temporal Analysis
  • Visual Cortex / metabolism*


  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 1