Synaptic activation of kainate receptors gates presynaptic CB(1) signaling at GABAergic synapses

Nat Neurosci. 2010 Feb;13(2):197-204. doi: 10.1038/nn.2481. Epub 2010 Jan 17.


Glutamate can control inhibitory synaptic transmission through activation of presynaptic kainate receptors. We found that glutamate released by train stimulation of Schaffer collaterals could lead to either short-term depression or short-term facilitation of inhibitory synaptic transmission in mouse CA1 pyramidal neurons, depending on the presence of cannabinoid type 1 (CB(1)) receptors on GABAergic afferents. The train-induced depression of inhibition (t-Di) required the mobilization of 2-arachidonoylglycerol through postsynaptic activation of metabotropic glutamate receptors and [Ca(2+)] rise. GluK1 (GluR5)-dependent depolarization of GABAergic terminals enabled t-Di by facilitating presynaptic CB(1) signaling. Thus, concerted activation of presynaptic CB(1) receptors and kainate receptors mediates short-term depression of inhibitory synaptic transmission. In contrast, in inhibitory connections expressing GluK1, but not CB(1), receptors, train stimulation of Schaffer collaterals led to short-term facilitation. Thus, activation of kainate receptors by synaptically released glutamate gates presynaptic CB(1) signaling, which in turn controls the direction of short-term heterosynaptic plasticity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism
  • CA1 Region, Hippocampal / physiology
  • Calcium / metabolism
  • Endocannabinoids
  • Glutamic Acid / metabolism
  • Glycerides / metabolism
  • In Vitro Techniques
  • Mice
  • Mice, Transgenic
  • Neural Inhibition / physiology
  • Neuronal Plasticity / physiology*
  • Presynaptic Terminals / physiology*
  • Pyramidal Cells / physiology
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Receptors, Kainic Acid / genetics
  • Receptors, Kainic Acid / metabolism*
  • Receptors, Metabotropic Glutamate / metabolism
  • Synapses / physiology*
  • Synaptic Transmission / physiology
  • Time Factors
  • gamma-Aminobutyric Acid / metabolism*


  • Arachidonic Acids
  • Endocannabinoids
  • Gluk1 kainate receptor
  • Glycerides
  • Receptor, Cannabinoid, CB1
  • Receptors, Kainic Acid
  • Receptors, Metabotropic Glutamate
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • glyceryl 2-arachidonate
  • Calcium