Neonatal phenobarbital exposure disrupts GABAergic synaptic maturation in rat CA1 neurons

Epilepsia
Nour Al-MuhtasibPatrick A Forcelli

Abstract

Phenobarbital is the most commonly utilized drug for the treatment of neonatal seizures. The use of phenobarbital continues despite growing evidence that it exerts suboptimal seizure control and is associated with long-term alterations in brain structure, function, and behavior. Alterations following neonatal phenobarbital exposure include acute induction of neuronal apoptosis, disruption of synaptic development in the striatum, and a host of behavioral deficits. These behavioral deficits include those in learning and memory mediated by the hippocampus. However, the synaptic changes caused by acute exposure to phenobarbital that lead to lasting effects on brain function and behavior remain understudied. Postnatal day (P)7 rat pups were treated with phenobarbital (75 mg/kg) or saline. On P13-14 or P29-37, acute slices were prepared and whole-cell patch-clamp recordings were made from CA1 pyramidal neurons. At P14 we found an increase in miniature inhibitory postsynaptic current (mIPSC) frequency in the phenobarbital-exposed as compared to the saline-exposed group. In addition to this change in mIPSC frequency, the phenobarbital group displayed larger bicuculline-sensitive tonic currents, decreased capacitance and membrane time c...Continue Reading

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Citations

Feb 19, 2019·Current Treatment Options in Neurology·Stephanie AhrensLaurel A Slaughter
Dec 12, 2020·Cells·Aisling Leavy, Eva M Jimenez Mateos
Jan 30, 2021·Frontiers in Behavioral Neuroscience·Angélica Vega-GarcíaSandra Orozco-Suárez
Jan 12, 2019·Neuropharmacology·Megan N HuizengaPatrick A Forcelli
Aug 14, 2021·Neurotherapeutics : the Journal of the American Society for Experimental NeuroTherapeutics·Julie M ZiobroRenée A Shellhaas

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