Hyperbaric Hyperoxia and Normobaric Reoxygenation Increase Excitability and Activate Oxygen-Induced Potentiation in CA1 Hippocampal Neurons

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 O ₂ toxicity, which presents as seizures. We tested the hypothesis that excitability increases in CA1 neurons of the rat hippocampal slice (400 μm) over a continuum of hyperoxia that spans normobaric and hyperbaric pressures. Amplitude changes of the orthodromic population spike were used to assess neuronal O ₂ sensitivity before, during, and following exposure to 0, 0.6, 0.95 (control), 2.84, and 4.54 atmospheres absolute (ATA) O ₂ . Polarographic O ₂ electrodes were used to measure tissue slice PO ₂ (Pt _{O 2} ). In 0.95 ATA O ₂ , core Pt _{O 2} at 200 μm deep was 115 ± 16 Torr (mean ± SE). Increasing O ₂ to 2.84 and 4.54 ATA increased core Pt _{O 2} 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 O ₂ and hypoxia (0.00 ATA) decreased core Pt _{O 2} to 84 ± 6 and 20 ± 4 Torr, respectively, and abolished the orthodromic response. Reoxygenation from 0.0 or 0.6 ATA O ₂ , 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 Pt _{O 2} , 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.