Glia-dependent switch of kainate receptor presynaptic action

J Neurosci. 2010 Jan 20;30(3):985-95. doi: 10.1523/JNEUROSCI.3389-09.2010.


Presynaptic kainate receptors (KARs) exert a modulatory action on transmitter release. This effect can be switched from facilitation to inhibition by an increased concentration of KAR agonists. We here report that activation of presynaptic GluK1-containing KARs facilitates GABA release on oxytocin and vasopressin neurons in the supraoptic nucleus of the hypothalamus. Increase in ambient levels of glutamate associated with the physiological reduction of astrocytic coverage of oxytocin neurons in lactating rats switches this KAR-mediated facilitation to inhibition of GABAergic transmission. This effect was reproduced in both oxytocin and vasopressin neurons of virgin rats when glutamate transporters were blocked pharmacologically, thereby establishing that enhanced levels of extracellular glutamate induce the switch in KAR-mediated action. The facilitation of GABA release was inhibited with philanthotoxin, a Ca(2+)-permeable KAR antagonist, suggesting that this effect was associated with an ionotropic mode of action. Conversely, KAR-mediated inhibition was compromised in the presence of U73122, a phospholipase C inhibitor, in agreement with the involvement of a metabotropic pathway. We thus reveal that physiological astrocytic plasticity modifies the mode of action of presynaptic KARs, thereby inversing their coupling with GABA release.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Electric Stimulation / methods
  • Excitatory Amino Acid Agonists / pharmacology
  • Excitatory Amino Acid Antagonists / pharmacology
  • Glutamic Acid / metabolism
  • In Vitro Techniques
  • Inhibitory Postsynaptic Potentials / drug effects
  • Inhibitory Postsynaptic Potentials / physiology*
  • Kainic Acid / pharmacology
  • Lysine / analogs & derivatives
  • Lysine / metabolism
  • Neuroglia / drug effects
  • Neuroglia / physiology*
  • Neurons / cytology*
  • Patch-Clamp Techniques / methods
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Kainic Acid / agonists
  • Receptors, Kainic Acid / antagonists & inhibitors
  • Receptors, Kainic Acid / metabolism*
  • Suprachiasmatic Nucleus / cytology
  • gamma-Aminobutyric Acid / metabolism


  • Excitatory Amino Acid Agonists
  • Excitatory Amino Acid Antagonists
  • Gluk1 kainate receptor
  • Receptors, Kainic Acid
  • Glutamic Acid
  • gamma-Aminobutyric Acid
  • biocytin
  • Lysine
  • Kainic Acid