GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo

Knut Kirmse (), Michael Kummer, Yury Kovalchuk, Otto W. Witte, Olga Garaschuk and Knut Holthoff
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Knut Kirmse: University Hospital Jena
Michael Kummer: University Hospital Jena
Yury Kovalchuk: Institute of Physiology II, Eberhard-Karls University Tübingen
Otto W. Witte: University Hospital Jena
Olga Garaschuk: Institute of Physiology II, Eberhard-Karls University Tübingen
Knut Holthoff: University Hospital Jena

Nature Communications, 2015, vol. 6, issue 1, 1-13

Abstract: Abstract A large body of evidence from in vitro studies suggests that GABA is depolarizing during early postnatal development. However, the mode of GABA action in the intact developing brain is unknown. Here we examine the in vivo effects of GABA in cells of the upper cortical plate using a combination of electrophysiological and Ca2+-imaging techniques. We report that at postnatal days (P) 3–4, GABA depolarizes the majority of immature neurons in the occipital cortex of anaesthetized mice. At the same time, GABA does not efficiently activate voltage-gated Ca2+ channels and fails to induce action potential firing. Blocking GABAA receptors disinhibits spontaneous network activity, whereas allosteric activation of GABAA receptors has the opposite effect. In summary, our data provide evidence that in vivo GABA acts as a depolarizing neurotransmitter imposing an inhibitory control on network activity in the neonatal (P3–4) neocortex.

Date: 2015
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DOI: 10.1038/ncomms8750

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