title: Glial Calcium Waves are Triggered by Seizure Activity and Not Essential for Initiating Ictal Onset or Neurovascular Coupling.
abstract: It has been postulated that glia play a critical role in modifying neuronal activity, mediating neurovascular coupling, and in seizure initiation. We investigated the role of glia in ictogenesis and neurovascular coupling through wide-field multicell and 2-photon single cell imaging of calcium and intrinsic signal imaging of cerebral blood volume in an in vivo rat model of focal neocortical seizures. Ictal events triggered a slowly propagating glial calcium wave that was markedly delayed after both neuronal and hemodynamic onset. Glial calcium waves exhibited a stereotypical spread that terminated prior to seizure offset and propagated to an area ~60% greater than the propagation area of neural and vascular signals. Complete blockage of glial activity with fluoroacetate resulted in no change in either neuronal or hemodynamic activity. These ictal glial waves were blocked by carbenoxolone, a gap junction blocker. Our in vivo data reveal that ictal events trigger a slowly propagating, stereotypical glial calcium wave, mediated by gap junctions, that is spatially and temporally independent of neuronal and hemodynamic activities. We introduce a novel ictally triggered propagating glial calcium wave calling into question the criticality of glial calcium wave in both ictal onset and neurovascular coupling.
authors.affiliation: Department of Neurological Surgery, Feil Family Brain and Mind Research Institute, Sackler Brain and Spine Institute, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Eliza
authors.initials: E
authors.lastname: Baird-Daniel
authors.affiliation: Department of Neurological Surgery, Feil Family Brain and Mind Research Institute, Sackler Brain and Spine Institute, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Andy G S
authors.initials: AGS
authors.lastname: Daniel
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Wenzel
authors.affiliation: Department of Neurological Surgery, Feil Family Brain and Mind Research Institute, Sackler Brain and Spine Institute, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY 10065, USA.|Department of Radiology, First Hospital of Jilin University, Changchun, Jilin 130021, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Physiology and Cellular Biophysics, Columbia University, New York, NY 10032, USA.
authors.forename: Jyun-You
authors.initials: JY
authors.lastname: Liou
authors.affiliation: Department of Neurological Surgery, Feil Family Brain and Mind Research Institute, Sackler Brain and Spine Institute, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Philippe
authors.initials: P
authors.lastname: Laffont
authors.affiliation: Department of Neurological Surgery, Feil Family Brain and Mind Research Institute, Sackler Brain and Spine Institute, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Mingrui
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Biological Sciences, Columbia University, New York, NY 10027, USA.
authors.forename: Rafael
authors.initials: R
authors.lastname: Yuste
authors.affiliation: Department of Neurological Surgery, Feil Family Brain and Mind Research Institute, Sackler Brain and Spine Institute, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Ma
authors.affiliation: Department of Neurological Surgery, Feil Family Brain and Mind Research Institute, Sackler Brain and Spine Institute, Weill Cornell Medicine, New York-Presbyterian Hospital, New York, NY 10065, USA.
authors.forename: Theodore H
authors.initials: TH
authors.lastname: Schwartz
mesh_terms: D015761:4-Aminopyridine / Q000633:toxicity; D000818:Animals; D001931:Brain Mapping; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling; D002229:Carbenoxolone / Q000494:pharmacology; D003952:Diagnostic Imaging; D004195:Disease Models, Animal; D004827:Epilepsy / Q000139:chemically induced / Q000473:pathology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects / Q000502:physiology; D008297:Male; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D000069336:Neurovascular Coupling / Q000502:physiology*; D026902:Potassium Channel Blockers / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D026941:Sodium Channel Blockers / Q000494:pharmacology; D013003:Somatosensory Cortex / Q000503:physiopathology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D026941:Sodium Channel Blockers; D013779:Tetrodotoxin; D015761:4-Aminopyridine; D002229:Carbenoxolone; D002118:Calcium
keywords: epilepsy; glia; ictogenesis; neurovascular coupling; optical imaging