Oxygen and seizure dynamics: I. experiments

Justin Ingram, Chunfeng Zhang, John R. Cressman, Anupam Hazra, Yina Wei, Yong Eun Koo, Jokubas Žiburkus, Raoul Kopelman, Jian Xu, Steven J. Schiff

Research output: Contribution to journalArticlepeer-review

26 Scopus citations

Abstract

We utilized a novel ratiometric nanoquantum dot fluorescence resonance energy transfer (NQD-FRET) optical sensor to quantitatively measure oxygen dynamics from single cell microdomains during hypoxic episodes as well as during 4-aminopyridine (4-AP)-induced spontaneous seizure- like events in rat hippocampal slices. Coupling oxygen sensing with electrical recordings, we found the greatest reduction in the O2 concentration ([O2]) in the densely packed cell body stratum (st.) pyramidale layer of the CA1 and differential layer-specific O2 dynamics between the st. pyramidale and st. oriens layers. These hypoxic decrements occurred up to several seconds before seizure onset could be electrically measured extracellularly. Without 4-AP, we quantified a narrow range of [O2], similar to the endogenous hypoxia found before epileptiform activity, which permits a quiescent network to enter into a seizure-like state. We demonstrated layerspecific patterns of O2 utilization accompanying layer-specific neuronal interplay in seizure. None of the oxygen overshoot artifacts seen with polarographic measurement techniques were observed. We therefore conclude that endogenously generated hypoxia may be more than just a consequence of increased cellular excitability but an influential and critical factor for orchestrating network dynamics associated with epileptiform activity.

Original languageEnglish (US)
Pages (from-to)205-212
Number of pages8
JournalJournal of neurophysiology
Volume112
Issue number2
DOIs
StatePublished - Jul 15 2014

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

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