Calcium Dynamics of Cortical Astrocytic Networks In Vivo

Abstract

Large and long-lasting cytosolic calcium surges in astrocytes have been described in cultured cells and acute slice preparations. The mechanisms that give rise to these calcium events have been extensively studied in vitro. However, their existence and functions in the intact brain are unknown. We have topically applied Fluo-4 AM on the cerebral cortex of anesthetized rats, and imaged cytosolic calcium fluctuation in astrocyte populations of superficial cortical layers in vivo, using two-photon laser scanning microscopy. Spontaneous [Ca2+]i events in individual astrocytes were similar to those observed in vitro. Coordination of [Ca2+]i events among astrocytes was indicated by the broad cross-correlograms. Increased neuronal discharge was associated with increased astrocytic [Ca2+]i activity in individual cells and a robust coordination of [Ca2+]i signals in neighboring astrocytes. These findings indicate potential neuron–glia communication in the intact brain.

Models of astrocytic Ca2+ dynamics and epilepsy

“…Hirase et al showed that in anesthesized rats, astrocytes exhibited [Ca 2+ ] i fluctuations [30] similar to those previously observed in astrocytes from cell cultures and slice tissues.…”

Enhanced Astrocytic Ca2+Signals Contribute to Neuronal Excitotoxicity after Status Epilepticus

“…After 45-60 min, excess dye was removed by irrigation with ACSF. As described (Hirase et al, 2004;Nimmerjahn et al, 2004), this protocol leads to the selective labeling of astrocytes with the Ca 2ϩ indicator, fluo-4. In some experiments, selectivity of labeling was confirmed using sulforhodamine 101 (SR101) (supplemental Fig.…”

“…Chemically induced epileptiform activity in brain slice preparations (Tian et al, 2005;Fellin et al, 2006) or in vivo (Hirase et al, 2004), in addition to evoking intense neuronal discharges, stimulates astrocytic Ca 2ϩ signals. We recently demonstrated that chemically induced epileptiform activity induces a prolonged increase in astrocytic Ca 2ϩ excitability that outlasts the period of epileptiform activity (Fellin et al, 2006), raising the potential for the excitability of the astrocyte to be altered in a long-term manner after seizure activity in vivo.…”

“…We recently demonstrated that chemically induced epileptiform activity induces a prolonged increase in astrocytic Ca 2ϩ excitability that outlasts the period of epileptiform activity (Fellin et al, 2006), raising the potential for the excitability of the astrocyte to be altered in a long-term manner after seizure activity in vivo. We directly tested this hypothesis by using two-photon imaging of astrocytic Ca 2ϩ (Hirase et al, 2004;Nimmerjahn et al, 2004) to ask whether seizures per se persistently modify the excitability of astrocytes. Layer 2/3 astrocytes in the barrel cortex were selectively loaded with the Ca 2ϩ indicator fluo-4 either before or 2 or more days after pilocarpineinduced SE (Nimmerjahn et al, 2004).…”

Different cellular sources and different roles of adenosine: A1 receptor-mediated inhibition through astrocytic-driven volume transmission and synapse-restricted A2A receptor-mediated facilitation of plasticity

“…Since this tonic adenosine level is derived from exocytotic release of gliotransmitters from astrocytes (Pascual et al, 2005), it is possible to assume that the endogenous extracellular adenosine is originated from ATP released from astrocytes (it should be noted that this conclusion is only an assumption still to be demonstrated: in fact, it remains possible that some gliotransmitter may indirectly cause the release of ATP and/or adenosine from neurons). Irrespective of the actual gliotransmitter that is indirectly responsible for the generation of endogenous extracellular adenosine, it should be pointed out that it is constitutively released in slices, albeit Ca 2+ waves, indicative of astrocytic activation (Dani et al, 1992;reviewed in Halassa et al, 2007;Scemes and Giaume, 2006), are scarcely observed upon low frequency stimulation of adult brain preparations (Hirase et al, 2004;Newman, 2003; see also Grosche et al, 1999;Pasti et al, 1997). But from the functional point of view, this astrocytic-driven constitutive generation of endogenous extracellular adenosine has an important correlate: it means that the tonic A 1 receptor-mediated inhibition of excitatory synaptic transmission is likely designed to act globally in brain circuits to decrease noise in excitatory circuits.…”