| Title | Differences in cortical versus subcortical GABAergic signaling: a candidate mechanism of electroclinical uncoupling of neonatal seizures. | | Author(s) | Glykys J, Dzhala VI, Kuchibhotla KV, Feng G, Kuner T, Augustine G, Bacskai BJ, Staley KJ | | Institution | Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02144, USA. | | Source | Neuron 2009 Sep 10; 63(5):657-72. | | MeSH | Amygdala
Animals
Animals, Newborn
Anticonvulsants
Bumetanide
Chlorides
Female
Male
Neocortex
Neurons
Phenobarbital
Rats
Rats, Sprague-Dawley
Receptors, GABA-A
Seizures
Sex Characteristics
Sodium Potassium Chloride Symporter Inhibitors
Sodium-Potassium-Chloride Symporters
Synaptic Transmission
Thalamus
gamma-Aminobutyric Acid
| | 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 GABA(A) receptor (GABA(A)R) conductance. The effects of GABA(A)R 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 GABA(A)R 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. | | Language | eng | | Pub Type(s) | In Vitro
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
| | PubMed ID | 19755108 |
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