Differences in Cortical versus Subcortical GABAergic Signaling: A Candidate Mechanism of Electroclinical Uncoupling of Neonatal Seizures

Joseph Glykys; Volodymyr I Dzhala; Kishore V Kuchibhotla; Guoping Feng; Thomas Kuner; George Augustine; Brian J Bacskai; Kevin J Staley

doi:10.1016/j.neuron.2009.08.022

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Differences in Cortical versus Subcortical GABAergic Signaling: A Candidate Mechanism of Electroclinical Uncoupling of Neonatal Seizures

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Differences in Cortical versus Subcortical GABAergic Signaling: A Candidate Mechanism of Electroclinical Uncoupling of Neonatal Seizures

Joseph Glykys, Volodymyr I Dzhala, Kishore V Kuchibhotla, Guoping Feng, Thomas Kuner, George Augustine, Brian J Bacskai and Kevin J Staley

Neuron (Cambridge, Mass.), Vol.63(5), pp.657-672

09/10/2009

DOI: 10.1016/j.neuron.2009.08.022

PMID: 19755108

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Abstract

Electroclinical uncoupling of neonatal seizures refers to electrographic seizure activity that is not clinically manifest. Uncoupling increases after treatment with Phenobarbital, which enhances the GABAA receptor (GABAAR) conductance. The effects of GABAAR activation depend on the intracellular Cl− concentration ([Cl−]i) that is determined by the inward Cl− transporter NKCC1 and the outward Cl− transporter KCC2. Differential maturation of Cl− transport observed in cortical versus subcortical regions should alter the efficacy of GABA-mediated inhibition. In perinatal rat pups, most thalamic neurons maintained low [Cl−]i and were inhibited by GABA. Phenobarbital suppressed thalamic seizure activity. Most neocortical neurons maintained higher [Cl−]i, and were excited by GABAAR activation. Phenobarbital had insignificant anticonvulsant responses in the neocortex until NKCC1 was blocked. Regional differences in the ontogeny of Cl− transport may thus explain why seizure activity in the cortex is not suppressed by anticonvulsants that block the transmission of seizure activity through subcortical networks.

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Title: Subtitle: Differences in Cortical versus Subcortical GABAergic Signaling: A Candidate Mechanism of Electroclinical Uncoupling of Neonatal Seizures
Creators: Joseph Glykys - Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA
Volodymyr I Dzhala - Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA
Kishore V Kuchibhotla - Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA
Guoping Feng - Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Thomas Kuner - Institute of Anatomy and Cell Biology, University of Heidelberg, 69120 Heidelberg, Germany
George Augustine - Department of Neurobiology, Duke University Medical Center, Durham, NC 27710, USA
Brian J Bacskai - Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA
Kevin J Staley - Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA
Resource Type: Journal article
Publication Details: Neuron (Cambridge, Mass.), Vol.63(5), pp.657-672
Publisher: Elsevier Inc
DOI: 10.1016/j.neuron.2009.08.022
PMID: 19755108
ISSN: 0896-6273
eISSN: 1097-4199
Language: English
Date published: 09/10/2009
Academic Unit: Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
Record Identifier: 9984014021602771

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