First Author | Shen W | Year | 2017 |
Journal | Sci Rep | Volume | 7 |
Issue | 1 | Pages | 11280 |
PubMed ID | 28900295 | Mgi Jnum | J:288983 |
Mgi Id | MGI:6435563 | Doi | 10.1038/s41598-017-11793-x |
Citation | Shen W, et al. (2017) An autocrine purinergic signaling controls astrocyte-induced neuronal excitation. Sci Rep 7(1):11280 |
abstractText | 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(2+) 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. |