An autocrine purinergic signaling controls astrocyte-induced neuronal excitation

Sci Rep. 2017 Sep 12;7(1):11280. doi: 10.1038/s41598-017-11793-x.

Abstract

Astrocyte-derived gliotransmitters glutamate and ATP modulate neuronal activity. It remains unclear, however, how astrocytes control the release and coordinate the actions of these gliotransmitters. Using transgenic expression of the light-sensitive channelrhodopsin 2 (ChR2) in astrocytes, we observed that photostimulation reliably increases action potential firing of hippocampal pyramidal neurons. This excitation relies primarily on a calcium-dependent glutamate release by astrocytes that activates neuronal extra-synaptic NMDA receptors. Remarkably, our results show that ChR2-induced Ca2+ increase and subsequent glutamate release are amplified by ATP/ADP-mediated autocrine activation of P2Y1 receptors on astrocytes. Thus, neuronal excitation is promoted by a synergistic action of glutamatergic and autocrine purinergic signaling in astrocytes. This new mechanism may be particularly relevant for pathological conditions in which ATP extracellular concentration is increased and acts as a major danger signal.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Action Potentials*
  • Adenosine Triphosphate / metabolism
  • Animals
  • Astrocytes / metabolism*
  • Autocrine Communication*
  • Calcium / metabolism
  • Calcium Signaling
  • Cell Communication*
  • Female
  • Male
  • Mice
  • Neurons / metabolism*
  • Purinergic Agents / metabolism
  • Receptors, N-Methyl-D-Aspartate / metabolism
  • Receptors, Purinergic / metabolism
  • Signal Transduction*

Substances

  • Purinergic Agents
  • Receptors, N-Methyl-D-Aspartate
  • Receptors, Purinergic
  • Adenosine Triphosphate
  • Calcium