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Enhanced synaptic activity and epileptiform events in the embryonic KCC2 deficient hippocampus

Item Type:Article
Title:Enhanced synaptic activity and epileptiform events in the embryonic KCC2 deficient hippocampus
Creators Name:Khalilov, I. and Chazal, G. and Chudotvorova, I. and Pellegrino, C. and Corby, S. and Ferrand, N. and Gubkina, O. and Nardou, R. and Tyzio, R. and Yamamoto, S. and Jentsch, T.J. and Huebner, C.A. and Gaiarsa, J.L. and Ben-Ari, Y. and Medina, I.
Abstract:The neuronal potassium-chloride co-transporter 2 [indicated thereafter as KCC2 (for protein) and Kcc2 (for gene)] is thought to play an important role in the post natal excitatory to inhibitory switch of GABA actions in the rodent hippocampus. Here, by studying hippocampi of wild-type (Kcc2(+/+)) and Kcc2 deficient (Kcc2(-/-)) mouse embryos, we unexpectedly found increased spontaneous neuronal network activity at E18.5, a developmental stage when KCC2 is thought not to be functional in the hippocampus. Embryonic Kcc2(-/-) hippocampi have also an augmented synapse density and a higher frequency of spontaneous glutamatergic and GABA-ergic postsynaptic currents than naïve age matched neurons. However, intracellular chloride concentration ([Cl(-)](i)) and the reversal potential of GABA-mediated currents (E(GABA)) were similar in embryonic Kcc2(+/+) and Kcc2(-/-) CA3 neurons. In addition, KCC2 immunolabeling was cytoplasmic in the majority of neurons suggesting that the molecule is not functional as a plasma membrane chloride co-transporter. Collectively, our results show that already at an embryonic stage, KCC2 controls the formation of synapses and, when deleted, the hippocampus has a higher density of GABA-ergic and glutamatergic synapses and generates spontaneous and evoked epileptiform activities. These results may be explained either by a small population of orchestrating neurons in which KCC2 operates early as a chloride exporter or by transporter independent actions of KCC2 that are instrumental in synapse formation and networks construction.
Keywords:GABA, KCC2, Neuron, Development, Synapse, Network, Animals, Mice
Source:Frontiers in Cellular Neuroscience
Publisher:Frontiers Media SA
Page Range:23
Date:1 November 2011
Official Publication:https://doi.org/10.3389/fncel.2011.00023
PubMed:View item in PubMed

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