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Updated: Aug 9, 2026
Electrophoretic Delivery of γ-aminobutyric Acid (GABA) into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
Selective impairment of GABAergic synaptic transmission in the flurothyl model of neonatal seizures
Elena Isaeva1, Dmytro Isaev, Rustem Khazipov
1Section of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, NH 03756, USA.
Insights
Neonatal seizures in rats selectively reduced inhibitory GABAergic synaptic responses. This depression may contribute to long-term cognitive deficits and altered seizure susceptibility observed after early-life seizures.
Area of Science:
- Neuroscience
- Developmental Neuroscience
- Neurophysiology
Background:
- Neonatal seizures have lasting negative effects on brain function, including memory.
- The impact of early-life seizures on developing synaptic transmission remains poorly understood.
- Understanding these changes is crucial for addressing long-term neurological consequences.
Purpose of the Study:
- To investigate how neonatal seizures affect GABAergic and glutamatergic synaptic transmission during early development in the rat hippocampus.
- To determine if seizures alter the developmental trajectory of synaptic signaling.
Main Methods:
- Induced seizures in rat pups using flurothyl during the first postnatal days.
- Utilized whole-cell patch-clamp and extracellular recordings in hippocampal slices.
- Examined spontaneous inhibitory and excitatory postsynaptic currents in CA3 pyramidal cells.
Main Results:
- A 27% decrease in the amplitude of spontaneous inhibitory postsynaptic currents was observed at postnatal days 15-17 in seizure-exposed rats.
- No significant alterations were found in the frequency or kinetics of inhibitory postsynaptic currents.
- Glutamatergic synaptic transmission, including AMPA and NMDA receptor-mediated currents, remained unaffected by neonatal seizures.
Conclusions:
- Neonatal seizures selectively depress the amplitude of GABAergic synaptic responses in the developing hippocampus.
- This selective depression of inhibitory signaling may underlie the adverse neurological and behavioral outcomes following early-life seizures.
- Further research is needed to elucidate the precise mechanisms linking seizure-induced synaptic changes to long-term deficits.
Abstract:
Neonatal seizures can result in long-term adverse consequences including alteration of seizure susceptibility and impairment in spatial memory. However, little is known about the effects of neonatal seizures on developmental changes occurring in synaptic transmission during the first postnatal weeks. The purpose of the present study was to examine the effect of neonatal seizures on several aspects of gamma-aminobutyric acid (GABA)ergic and glutamatergic synaptic transmission in the developing rat hippocampus. Flurothyl was used to induce multiple recurrent seizures in rat pups during the first postnatal days. Whole-cell patch-clamp recordings from the hippocampal CA3 pyramidal cell and extracellular recordings from the CA3 pyramidal cell layer were made in slice preparations. In rats that experienced neonatal seizures the amplitude of spontaneous inhibitory postsynaptic currents at P15-17 was decreased by 27% compared with controls, whereas neither frequency nor the kinetic properties were altered. Neonatal seizures did not affect the timing of the developmental switch in the GABAA signaling from excitatory to inhibitory. None of the studied parameters of glutamatergic postsynaptic currents was different between the flurothyl and control groups, including the amplitude and frequency of the spontaneous excitatory postsynaptic currents, the ratio of the amplitudes and frequencies of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and N-methyl-D-aspartate (NMDA)-mediated spontaneous postsynaptic currents, and the kinetics of AMPA and NMDA mediated postsynaptic currents in the age groups P8-10 and P15-17. We suggest that the selective depression of the amplitude of GABAergic synaptic responses may contribute to the adverse neurological and behavioral consequences that occur following neonatal seizures.
