Microglial calcium signal acts as a rapid sensor of single neuron damage in vivo.
In the healthy adult brain microglia, the main immune-competent cells of the CNS, have a distinct (so-called resting or surveying) phenotype. Resting microglia can only be studied in vivo since any isolation of brain tissue inevitably triggers microglial activation. Here we used in vivo two-photon imaging to obtain a first insight into Ca(2+) signaling in resting cortical microglia. The majority (80%) of microglial cells showed no spontaneous Ca(2+) transients at rest and in conditions of strong neuronal activity. However, they reliably responded with large, generalized Ca(2+) transients to damage of an individual neuron. These damage-induced responses had a short latency (0.4-4s) and were localized to the immediate vicinity of the damaged neuron (< 50 μm cell body-to-cell body distance). They were occluded by the application of ATPγS as well as UDP and 2-MeSADP, the agonists of metabotropic P2Y receptors, and they required Ca(2+) release from the intracellular Ca(2+) stores. Thus, our in vivo data suggest that microglial Ca(2+) signals occur mostly under pathological conditions and identify a Ca(2+) store-operated signal, which represents a very sensitive, rapid, and highly localized response of microglial cells to brain damage. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.
Institute of Physiology II, University of Tübingen, Keplerstr. 15, 72074 Tübingen, Germany.
Gerhard
G
Eichhoff
Bianca
B
Brawek
Olga
O
Garaschuk
D000818:Animals; D020013:Calcium Signaling; D021621:Imaging, Three-Dimensional; D051379:Mice; D017628:Microglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology*