Norepinephrine triggers release of glial ATP to increase postsynaptic efficacy

Nat Neurosci. 2005 Aug;8(8):1078-86. doi: 10.1038/nn1498. Epub 2005 Jul 3.


Glial cells actively participate in synaptic transmission. They clear molecules from the synaptic cleft, receive signals from neurons and, in turn, release molecules that can modulate signaling between neuronal elements. Whether glial-derived transmitters can contribute to enduring changes in postsynaptic efficacy, however, remains to be established. In rat hypothalamic paraventricular nucleus, we demonstrate an increase in the amplitude of miniature excitatory postsynaptic currents in response to norepinephrine that requires the release of ATP from glial cells. The increase in quantal efficacy, which likely results from an insertion of AMPA receptors, is secondary to the activation of P2X(7) receptors, an increase in postsynaptic calcium and the activation of phosphatidylinositol 3-kinase. The gliotransmitter ATP, therefore, contributes directly to the regulation of postsynaptic efficacy at glutamatergic synapses in the CNS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism*
  • Animals
  • Biomarkers / metabolism
  • Calcium / metabolism
  • Enzyme Activation
  • Excitatory Postsynaptic Potentials / drug effects
  • Excitatory Postsynaptic Potentials / physiology
  • In Vitro Techniques
  • Male
  • Neuroglia / drug effects*
  • Neuroglia / metabolism*
  • Neuroglia / physiology
  • Norepinephrine / pharmacology*
  • Paraventricular Hypothalamic Nucleus / cytology
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / physiology
  • Phosphatidylinositol 3-Kinases / metabolism
  • Rats
  • Rats, Long-Evans
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism
  • Receptors, Adrenergic, alpha-1 / metabolism
  • Receptors, Purinergic P2 / metabolism
  • Receptors, Purinergic P2X7
  • Synapses / metabolism
  • Synapses / physiology*
  • Tissue Distribution


  • Biomarkers
  • P2rx7 protein, rat
  • Receptors, AMPA
  • Receptors, Adrenergic, alpha-1
  • Receptors, Purinergic P2
  • Receptors, Purinergic P2X7
  • Adenosine Triphosphate
  • Phosphatidylinositol 3-Kinases
  • Calcium
  • Norepinephrine