Hyperoxic Stimulation of Synchronous Orthodromic Activity and Induction of Neural Plasticity Does Not Require Changes in Excitatory Synaptic Transmission

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hyperbaric oxygen, oxygen toxicity, synaptic transmission, oxygen-induced potentiation, oxidative stress

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The first study, described in the companion article, reports that acute exposure of rat hippocampal slices to either hyperbaric oxygen (HBO: 2.84 and 4.54 atmospheres absolute, ATA) or normobaric reoxygenation (NBOreox; i.e., normobaric hyperoxia: 0.6 or 0.0 → 0.95 ATA) stimulates synchronous orthodromic activity in CA1 neurons, which includes activation of O2-induced potentiation (OxIP) and, in some cases, hyperexcitability (secondary population spikes, sPS). In this second study we tested the hypothesis that HBO and NBOreox increase orthodromic activity of CA1 neurons (oPS, orthodromic population spike) and OxIP via a combination of both increased excitatory synaptic transmission (field excitatory postsynaptic potential, fEPSP) and intrinsic excitability (antidromic population spike, aPS). HBO and NBOreox increased the oPS but rarely increased or potentiated the fEPSP. HBO exposure produced epileptiform antidromic activity, which was abolished during inhibition of fast GABAergic and glutamatergic synaptic transmission. Decreasing O2 from 0.95 ATA (control) to 0.6 ATA (intermediate O2) or 0.0 ATA (hypoxia) reversibly abolished the fEPSP, and reoxygenation rarely induced potentiation of the fEPSP or aPS. Intracellular recordings and antidromic field potential recordings, however, revealed that synaptic transmission and neuronal excitability were preserved, albeit at lower levels, in 0.60 ATA O2. Together, these data indicate that 1) the changes in excitatory postsynaptic activity are not required for stimulation of the oPS during and HBO/NBOreox or for activation of OxIP, suggesting the latter is a form of intrinsic plasticity; 2) HBO disinhibits spontaneous synaptic transmission to induce epileptiform activity; and 3) although synchronous synaptic activation of the CA1 neuronal population requires hyperoxia (i.e., 0.95 ATA O2), synaptic activation of individual CA1 neurons does not.

our companion study (9) describes the excitatory effects of an acute hyperoxic stimulus, applied over a broad range of barometric pressure, on the orthodromic population spike (oPS) of CA1 neurons in rat hippocampal slices. Sensitivity to hyperbaric hyperoxia (hyperbaric oxygen, HBO) and normobaric hyperoxia (NBOreox; reoxygenation following acute exposure to hypoxia or an intermediate level of O2), was characterized by an increased amplitude of the oPS. In addition, both forms of hyperoxia led to the sustained (≤46 min) elevation in orthodromic excitability following exposure to HBO or NBOreox, referred to as “O2-induced potentiation” (OxIP), and could induce hyperexcitability (i.e., secondary population spikes, sPS). Thus CA1 neuronal excitability increases with increasing brain tissue Po2 (PtO2) at normobaric and hyperbaric pressures and persists beyond the period of hyperoxic exposure.

In the present study we tested the hypothesis that both NBOreox and HBO elevate orthodromic excitability in CA1 neurons, including activation of OxIP and induction of sPS activity, via mechanisms involving an increase in both excitatory synaptic transmission and postsynaptic excitability. Accordingly, we measured changes in the field excitatory postsynaptic potential (fEPSP) activated orthodromically by Schaffer collateral stimulation during O2 manipulation. To assess changes in postsynaptic excitability during O2 manipulation, we measured changes in the antidromic population spike (aPS) resulting from electrical stimulation of the axons of CA1 neurons. In addition, intracellular recordings were made in selected experiments to determine whether synaptic transmission was maintained in individual CA1 neurons exposed to an intermediate level of O2.

Our findings indicate that an increase in the fEPSP is not required for stimulation of the oPS during HBO or induction of OxIP during and following HBO or NBOreox. These findings suggest that OxIP is a form of intrinsic neural plasticity rather than synaptic plasticity. HBO, however, can induce mild epileptiform activity (i.e., sPS) in CA1 neurons by reduction in spontaneous inhibitory synaptic input, since sPS can be induced by blockade of GABA receptors alone. Therefore, the increased orthodromic excitability in CA1 neurons caused by HBO and NBOreox appears to involve changes in both intrinsic neuronal mechanisms (O2-induced stimulation of the oPS and induction of OxIP) and alterations in spontaneous synaptic activity (sPS during antidromic recordings). In addition, our findings indicate that synchronized synaptic activation of the population of CA1 neurons is contingent on the condition of normobaric hyperoxia (0.95 ATA).1 Conversely, synaptic activation of an individual CA1 neuron is not, which is maintained in an intermediate level of O2 (0.6 ATA).

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Citation / Publisher Attribution

Journal of Applied Physiology, v. 109, issue 3, p. 820-829