title: Enhanced Synaptic Activity and Epileptiform Events in the Embryonic KCC2 Deficient Hippocampus.
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.
authors: INSERM Unité 901 Marseille, France.
authors: Ilgam
authors: I
authors: Khalilov
authors: Geneviève
authors: G
authors: Chazal
authors: Ilona
authors: I
authors: Chudotvorova
authors: Christophe
authors: C
authors: Pellegrino
authors: Séverine
authors: S
authors: Corby
authors: Nadine
authors: N
authors: Ferrand
authors: Olena
authors: O
authors: Gubkina
authors: Romain
authors: R
authors: Nardou
authors: Roman
authors: R
authors: Tyzio
authors: Sumii
authors: S
authors: Yamamoto
authors: Thomas J
authors: TJ
authors: Jentsch
authors: Christian A
authors: CA
authors: Hübner
authors: Jean-Luc
authors: JL
authors: Gaiarsa
authors: Yehezkel
authors: Y
authors: Ben-Ari
authors: Igor
authors: I
authors: Medina