TABLE 1.

Key publications investigating the roles of astrocytic Ca^{2 +} signalling in ictogenesis and epileptogenesis.

Publication	Model	Ca2+ indicator	Main findings
Astrocytic Ca2+ signaling in ictogenesis
Kang et al., 2005	Rat hippocampal slices, 4-AP	Fluo-4 AM	Adding IP3 in astrocytes causes epileptiform activity due to glutamate, and that astrocytic Ca2+ signals occur during 4-AP seizures
Tian et al., 2005	Rat hippocampal slices: 4-AP, zero-Mg2+, bicuculline, penicillin Mouse cortex, in vivo, anesthetized: local injection of 4-AP	Fluo-4 AM	Increased astrocytic Ca2+ signaling in vivo during spread of 4-AP seizures, as well as showing that uncaging Ca2+ in astrocytes and extrasynaptic sources of glutamate triggered paroxysmal depolarization shifts
Fellin et al., 2006	Mouse cortical-hippocampal slices: zero-Mg2+ and picrotoxin, or 0.5 mM Mg2+ and 8.5 mM K+	Indo-1 AM or OGB-1 AM	A correlation between astrocytic Ca2+ and SICs, but activation of extrasynaptic NMDA activation by astrocytes is not necessary for either ictal or interictal epileptiform events
Ding et al., 2007	Mouse, in vivo, anesthetized. Pilocarpine s.c., 350 mg/kg	Fluo-4 AM	Increase in astrocytic Ca2+ signals during SE. See also under “Epileptogenesis”
Gómez-Gonzalo et al., 2010	Mouse entorhinal cortex slice: Picrotoxin/zero-Mg2+ Whole guinea pig: Bicuculline	OGB-1 AM / Rhod-2	Astrocytic Ca2+ signals are triggered by ictal but not interictal events, and can be inhibited by blocking mGluRs and purinergic receptors. Astrocytic Ca2+ signals contribute to the excitation of neurons, and blocking of early ictal astrocytic Ca2+ signals prevent spread of ictal activity.
Baird-Daniel et al., 2017	Rat cortex, in vivo, anesthetized. 4-AP. Blocking astrocytic Ca2+ signals and gap junctions with fluoroacetate and carbenoxolone, respectively	OGB-1 AM or Rhod-2 AM	Increased Ca2+ signals in astrocytes during seizures, but blocking of these did not affect epileptiform discharges or vascular dynamics associated with the seizures
Heuser et al., 2018	Mouse hippocampus, in vivo, unanesthetized, “dual color” Ca2+ imaging of hippocampal neurons and astrocytes	GCaMP6f in astrocytes	Prominent astrocytic Ca2+ activity preceding local neuronal recruitment to seizure activity in hippocampus
Diaz Verdugo et al., 2019	Zebra fish: PTZ	GCaMP6s in astrocytes	Large activations of astrocytic Ca2+ signals in the pre-ictal state and that astrocytic Ca2+ signals contribute to excitation of neurons
Zhang et al., 2019	Mouse cortex, in vivo, anesthetized: local injection of 4-AP	OGB-1 AM	Absolute levels of Ca2+ in the astrocytic endfeet correlates with vascular tone during seizures
Astrocytic calcium signaling in epileptogenesis
Ding et al., 2007	Mouse cortex, in vivo, anesthetized: Pilocarpine s.c. 350 mg/kg. 3D post SE	Fluo-4 AM	An increase in astrocytic Ca2+ signals at day 3 after SE due to mGluR5 signaling. Blocking this hyperactivity attenuated neuronal death
Szokol et al., 2015	Mouse hippocampal slices: intracortical kainate injection. Early epileptogenesis (1, 3, and 7 days after SE)	GCaMP5E	Increased Ca2+ signaling in hippocampal astrocytes upon schaffer collateral stimulation at days 1 and 3 after SE mediated by mGluR
Umpierre et al., 2019	Mouse hippocampal slices, at 1–3, 7–9, or 28–30 days after SE	GCaMP5G	mGluR5-mediated Ca2+ signaling re-emerges in epileptogenesis
Mentioned in Shigetomi et al. (2019): Sato et al.: unpublished report	4 weeks after pilocarpine induced SE	Not known	Increased Ca2+ signaling in reactive astrocytes
Enger et al., 2015 conference proceedings, American Epilepsy Society conference	Mouse hippocampus, in vivo, unanesthetized. Chronic MTLE model of deep cortical kainate injection, imaging at 3 months after SE	GCaMP6f	Episodic spontaneous hyperactivity of reactive astrocytes within/close to the sclerotic hippocampus
Plata et al., 2018	Rat, hippocampal slices, Lithium-pilocarpine	OGB-1 AM	A reduction in large size astrocytic Ca2+ events in atrophic astrocytes