Hyperbaric hyperoxia and normobaric reoxygenation increase excitability and activate oxygen-induced potentiation in CA1 hippocampal neurons

Abstract

Breathing hyperbaric oxygen (HBO) is common practice in hyperbaric and diving medicine. The benefits of breathing HBO, however, are limited by the risk of central nervous system O2 toxicity, which presents as seizures. We tested the hypothesis that excitability increases in CA1 neurons of the rat hippocampal slice (400 microm) over a continuum of hyperoxia that spans normobaric and hyperbaric pressures. Amplitude changes of the orthodromic population spike were used to assess neuronal O2 sensitivity before, during, and following exposure to 0, 0.6, 0.95 (control), 2.84, and 4.54 atmospheres absolute (ATA) O2. Polarographic O2 electrodes were used to measure tissue slice PO2 (PtO2). In 0.95 ATA O2, core PtO2 at 200 microm deep was 115±16 Torr (mean±SE). Increasing O2 to 2.84 and 4.54 ATA increased core PtO2 to 1,222±77 and 2,037±157 Torr, respectively. HBO increased the orthodromic population spike amplitude and usually induced hyperexcitability (i.e., secondary population spikes) and, in addition, a long-lasting potentiation of the orthodromic population spike that we have termed "oxygen-induced potentiation" (OxIP). Exposure to 0.60 ATA O2 and hypoxia (0.00 ATA) decreased core PtO2 to 84±6 and 20±4 Torr, respectively, and abolished the orthodromic response. Reoxygenation from 0.0 or 0.6 ATA O2, however, usually produced a response similar to that of HBO: hyperexcitability and activation of OxIP. We conclude that CA1 neurons exhibit increased excitability and neural plasticity over a broad range of PtO2, which can be activated by a single, hyperoxic stimulus. We postulate that transient acute hyperoxia stimulus, whether caused by breathing HBO or reoxygenation following hypoxia (e.g., disordered breathing), is a powerful stimulant for orthodromic activity and neural plasticity in the CA1 hippocampus.

Lactate Effectively Covers Energy Demands during Neuronal Network Activity in Neonatal Hippocampal Slices

“…In slices of mature animals, it has been shown that the efficacy of synaptic functioning (Garcia III et al, 2010) and network activity (Hajos et al, 2009) correlates strongly with the level of tissue oxygenation. Whether synaptic function in the neonatal network depends significantly on oxidative metabolism or whether its energy needs can be covered by glycolysis alone is unclear.…”

Graded Reductions in Oxygenation Evoke Graded Reconfiguration of the Isolated Respiratory Network

“…Neural tissue O 2 -depth profiles have been previously reported in vivo (for summary see Garcia 3rd et al 2010), in situ in the working heart-brain stem preparation (Wilson et al 2001), as well as in vitro in both isolated brain stem-spinal cord preparations (Brockhaus et al 1993;Okada et al 1993) and brain slices (Bingmann and Kolde 1982;Garcia 3rd et al 2010;Mulkey et al 2001). Several factors influence the degree of in vitro tissue oxygenation within a brain slice.…”

“…Although only a handful of brain slice studies have shown that neuronal activity is affected throughout a broad range of O 2 tensions outside of hypoxia (0% O 2 ) and the conventional control condition (95% O 2 ), these studies have shown that graded changes in O 2 , and not only hypoxia, can influence biochemical activity (D'Agostino 2007;Fowler 1993) and excitability of neurons within local networks (Fowler 1993;Garcia 3rd et al 2010;Hoffmann et al 2006;Mulkey et al 2001). Similarly, in invertebrate systems, small changes in oxygenation also have been shown to influence network activity (Clemens et al 2001).…”

Modulation of 4-aminopyridine-induced neuronal activity and local pO2 in rat hippocampal slices by changing the flow rate of the superfusion medium

“…By contrast, it was shown that hyperoxia leads to the activation of population spikes and synchronous interictal discharges in CA1 hippocampal region [18]. Oxygen-induced plasticity may play a substantial role in the pathogenesis of CNS.…”