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

Tools

Item Type:	Article
Title:	Enhanced synaptic activity and epileptiform events in the embryonic KCC2 deficient hippocampus
Creators Name:	Khalilov, I., Chazal, G., Chudotvorova, I., Pellegrino, C., Corby, S., Ferrand, N., Gubkina, O., Nardou, R., Tyzio, R., Yamamoto, S., Jentsch, T.J., Huebner, C.A., Gaiarsa, J.L., 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
ISSN:	1662-5102
Publisher:	Frontiers Media SA
Volume:	5
Page Range:	23
Date:	1 November 2011
Official Publication:	https://doi.org/10.3389/fncel.2011.00023
PubMed:	View item in PubMed

Repository Staff Only: item control page