| First Author | Shigetomi E | Year | 2018 |
| Journal | J Neurosci | Volume | 38 |
| Issue | 6 | Pages | 1383-1395 |
| PubMed ID | 29305530 | Mgi Jnum | J:276343 |
| Mgi Id | MGI:6116553 | Doi | 10.1523/JNEUROSCI.2625-17.2017 |
| Citation | Shigetomi E, et al. (2018) Role of Purinergic Receptor P2Y1 in Spatiotemporal Ca(2+) Dynamics in Astrocytes. J Neurosci 38(6):1383-1395 |
| abstractText | Fine processes of astrocytes enwrap synapses and are well positioned to sense neuronal information via synaptic transmission. In rodents, astrocyte processes sense synaptic transmission via Gq-protein coupled receptors (GqPCR), including the P2Y1 receptor (P2Y1R), to generate Ca(2+) signals. Astrocytes display numerous spontaneous microdomain Ca(2+) signals; however, it is not clear whether such signals are due to local synaptic transmission and/or in what timeframe astrocytes sense local synaptic transmission. To ask whether GqPCRs mediate microdomain Ca(2+) signals, we engineered mice (both sexes) to specifically overexpress P2Y1Rs in astrocytes, and we visualized Ca(2+) signals via a genetically encoded Ca(2+) indicator, GCaMP6f, in astrocytes from adult mice. Astrocytes overexpressing P2Y1Rs showed significantly larger Ca(2+) signals in response to exogenously applied ligand and to repetitive electrical stimulation of axons compared with controls. However, we found no evidence of increased microdomain Ca(2+) signals. Instead, Ca(2+) waves appeared and propagated to occupy areas that were up to 80-fold larger than microdomain Ca(2+) signals. These Ca(2+) waves accounted for only 2% of total Ca(2+) events, but they were 1.9-fold larger and 2.9-fold longer in duration than microdomain Ca(2+) signals at processes. Ca(2+) waves did not require action potentials for their generation and occurred in a probenecid-sensitive manner, indicating that the endogenous ligand for P2Y1R is elevated independently of synaptic transmission. Our data suggest that spontaneous microdomain Ca(2+) signals occur independently of P2Y1R activation and that astrocytes may not encode neuronal information in response to synaptic transmission at a point source of neurotransmitter release.SIGNIFICANCE STATEMENT Astrocytes are thought to enwrap synapses with their processes to receive neuronal information via Gq-protein coupled receptors (GqPCRs). Astrocyte processes display numerous microdomain Ca(2+) signals that occur spontaneously. To determine whether GqPCRs play a role in microdomain Ca(2+) signals and the timeframe in which astrocytes sense neuronal information, we engineered mice whose astrocytes specifically overexpress the P2Y1 receptor, a major GqPCR in astrocytes. We found that overexpression of P2Y1 receptors in astrocytes did not increase microdomain Ca(2+) signals in astrocyte processes but caused Ca(2+) wavelike signals. Our data indicate that spontaneous microdomain Ca(2+) signals do not require activation of P2Y1 receptors. |
