Distance-dependent scaling of AMPARs is cell-autonomous and GluA2 dependent

J Neurosci. 2013 Aug 14;33(33):13312-9. doi: 10.1523/JNEUROSCI.0678-13.2013.

Abstract

The extensive dendritic arbor of a pyramidal cell introduces considerable complexity to the integration of synaptic potentials. Propagation of dendritic potentials is largely passive, in contrast to regenerative axonal potentials that are maintained by voltage-gated sodium channels, leading to a declination in amplitude as dendritic potentials travel toward the soma in a manner that disproportionally affects distal synaptic inputs. To counteract this amplitude filtering, Schaffer collateral synapses onto CA1 pyramidal cells contain a varying number of AMPA receptors (AMPARs) per synapse that increases with distance from the soma, a phenomenon known as distance-dependent scaling. Here, we undertake an investigation into the molecular mechanisms of distance-dependent scaling. Using dendritic recordings from rat pyramidal neurons, we confirm the basic scaling phenomenon and find that it is expressed and can be manipulated cell autonomously. Finally, we show that it depends on the presence of both a reserve pool of AMPARs and the AMPAR subunit GluA2.

Publication types

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

MeSH terms

  • Animals
  • Blotting, Western
  • CA1 Region, Hippocampal / metabolism*
  • Cells, Cultured
  • Dendrites / metabolism*
  • Excitatory Postsynaptic Potentials / physiology
  • HEK293 Cells
  • Humans
  • Patch-Clamp Techniques
  • Pyramidal Cells / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, AMPA / biosynthesis*
  • Receptors, AMPA / metabolism
  • Synaptic Transmission / physiology

Substances

  • Receptors, AMPA
  • glutamate receptor ionotropic, AMPA 2