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NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development

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Item Type:Article
Title:NKCC1-dependent GABAergic excitation drives synaptic network maturation during early hippocampal development
Creators Name:Pfeffer, C.K. and Stein, V. and Keating, D.J. and Maier, H. and Rinke, I. and Rudhard, Y. and Hentschke, M. and Rune, G.M. and Jentsch, T.J. and Huebner, C.A.
Abstract:A high intracellular chloride concentration in immature neurons leads to a depolarizing action of GABA that is thought to shape the developing neuronal network. We show that GABA-triggered depolarization and Ca2+ transients were attenuated in mice deficient for the Na-K-2Cl cotransporter NKCC1. Correlated Ca2+ transients and giant depolarizing potentials (GDPs) were drastically reduced and the maturation of the glutamatergic and GABAergic transmission in CA1 delayed. Brain morphology, synaptic density, and expression levels of certain developmental marker genes were unchanged. The expression of lynx1, a protein known to dampen network activity, was decreased. In mice deficient for the neuronal Cl(-)/HCO(3)(-) exchanger AE3, GDPs were also diminished. These data show that NKCC1-mediated Cl(-) accumulation contributes to GABAergic excitation and network activity during early postnatal development and thus facilitates the maturation of excitatory and inhibitory synapses.
Keywords:Newborn Animals, Excitatory Postsynaptic Potentials, Hippocampus, Inbred C57BL Mice, Knockout Mice, Nerve Net, Sodium-Potassium-Chloride Symporters, Synapses, gamma-Aminobutyric Acid, Animals, Mice
Source:Journal of Neuroscience
ISSN:0270-6474
Publisher:Society for Neuroscience (U.S.A.)
Volume:29
Number:11
Page Range:3419-3430
Date:18 March 2009
Additional Information:Copyright (c) 2009 by The Society for Neuroscience
Official Publication:https://doi.org/10.1523/JNEUROSCI.1377-08.2009
PubMed:View item in PubMed

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