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Continuous Video Electroencephalogram during Hypoxia-Ischemia in Neonatal Mice
Published on: June 11, 2020
Decreased IH in hippocampal area CA1 pyramidal neurons after perinatal seizure-inducing hypoxia
Kun Zhang1, Bi-wen Peng, Russell M Sanchez
1Department of Pharmacology and Center for Biomedical Neuroscience, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
Insights
Neonatal seizures from hypoxia persistently decrease the hyperpolarization-activated cation current (IH) in hippocampal neurons. This reduction may contribute to epileptogenesis, with seizure effects varying by cause, not just age.
Area of Science:
- Neuroscience
- Epileptology
- Cellular Electrophysiology
Background:
- The hyperpolarization-activated cation current (IH) is crucial for neuronal excitability and synaptic integration in limbic circuits.
- Altered IH function is implicated in epileptogenesis, with differential changes observed following various seizure types and in different age groups.
- Previous studies show decreased IH after kainate-induced seizures in adult rats and increased IH after hyperthermia-induced seizures in neonatal rat pups.
Purpose of the Study:
- To investigate the impact of seizure-inducing global hypoxia on IH in neonatal rat hippocampal CA1 pyramidal neurons.
- To determine if and how IH is altered following neonatal hypoxic seizures.
Main Methods:
- Seizures were induced in neonatal rats (postnatal day 10) via brief exposure to hypoxia (5-7% O2).
- Whole-cell patch-clamp recordings were performed on hippocampal CA1 pyramidal neurons 30 minutes to 3 days post-hypoxia.
- IH was isolated using voltage-clamp and the specific blocker ZD 7288.
Main Results:
- A significant decrease in IH was observed in CA1 pyramidal neurons from hypoxia-treated rats compared to controls.
- No significant differences were found between groups in the voltage dependence or activation kinetics of IH.
- The observed decrease in IH persisted for up to 3 days after the hypoxic seizure episode.
Conclusions:
- Neonatal seizures induced by hypoxia can lead to a persistent reduction in IH in hippocampal CA1 pyramidal neurons.
- This persistent decrease in IH represents a potential mechanism contributing to epileptogenesis following neonatal hypoxic seizures.
- The effect of seizures on IH may be more dependent on the specific cause (etiology) of the seizure than on the developmental stage of the brain.
Purpose:
The hyperpolarization-activated cation current (IH) has been proposed to play a role in some forms of epileptogenesis, as it critically regulates synaptic integration and intrinsic excitability of principal limbic neurons and can be pathologically altered after experimentally induced seizures. In hippocampal CA1 pyramidal neurons, IH is functionally decreased after kainate-induced status epilepticus in adult rats but is increased after hyperthermia-induced seizures in immature rat pups. This study aimed to determine whether and how IH may be altered in CA1 pyramidal neurons after seizure-inducing global hypoxia in the neonatal brain.
Methods:
Seizures were induced in rat pups on postnatal day 10 by 14- to 16-min exposure to 5-7% O2. Whole-cell patch-clamp recordings were obtained from hippocampal CA1 pyramidal neurons in slices 30 min to 3 days after hypoxia treatment, and from control age-matched littermates. IH was isolated under voltage-clamp by subtracting current responses to hyperpolarizing voltage steps before and during application of the IH blocker ZD 7288 (100 microM).
Results:
IH was significantly decreased in pyramidal neurons from the hypoxia-treated group compared with controls (p<0.001; 19 controls; 15 hypoxia). Analyses of tail currents and activation kinetics indicated no statistically significant differences between groups in the voltage dependence or time constants of activation.
Conclusions:
These data indicate that a single episode of neonatal hypoxia that induces seizures can persistently decrease IH in CA1 pyramidal neurons, raising this as a potential contributing mechanism to epileptogenesis in this setting. Our findings further indicate that the consequences of seizures for IH may depend more on seizure etiology than on maturational stage.
