An Autocrine Purinergic Signaling Controls Astrocyte-induced Neuronal Excitation

Overview

Journal Sci Rep

Specialty Science

Date 2017 Sep 14

PMID 28900295

Citations 20

Authors

Weida Shen

Ljiljana Nikolic

Claire Meunier

Frank Pfrieger

Etienne Audinat

Affiliations

Soon will be listed here.

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 Ca 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.

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