Modulation of 4-aminopyridine-induced neuronal activity and local pO2 in rat hippocampal slices by changing the flow rate of the superfusion medium
V.G. Sydorenko, O.S. Komarov, B.S. Sushko, A.K. Romanov, E.V. Isaeva, D.S. Isaev
O. O. Bogomoletz Institute of Physiology, National Academy of Science, Ukraine, Kyiv
DOI: https://doi.org/10.15407/fz62.04.003
Abstract
The brain slice preparation is the most frequently used tool for testing of pharmacological agents on the
neuronal excitability. However, in the absence of blood circulation in vitro, the tissue oxygenation strongly
depends on the experimental conditions. It is well established that both hypoxia as well as hyperoxia can
modulate the neuronal network activity. Thereby changes in tissue oxygen level during experiment may
affect the final result. In the present study we investigated the effect of oxygenation on seizure susceptibility
in the hippocampal slice preparation using 4-aminopyridine (4-AP) model of ictogenesis in immature
rats. We found that changing the medium perfusion rate in the range of 1-5 ml/min greatly affects the tissue
oxygenation, amplitude and frequency of 4-AP-induced synchronous neuronal activity. The decrease in the
flow rate as well as substitution of the oxygen in the extracellular medium with nitrogen causes a strong
reduction of 4-AP-induced synchronous neuronal discharges. Our results demonstrate a significant linear
correlation between the power of 4-AP-induced neuronal activity and the oxygen level in slice tissue. Also
we demonstrated that the presence of medium flow is a necessary condition to support the constant level
of the slice oxygenation. These data suggest that the oxygen supply of the brain slice strongly depends on
experimental protocol and could modulate in vitro neuronal network excitability which should be taken
into consideration when planning epilepsy-related studies.
Keywords:
brain slices; synchronous neuronal activity; oxygen; local field potential
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