Frontiers in Cellular Neuroscience (Nov 2011)

Enhanced synaptic activity and epileptiform events in the embryonic Kcc2 deficient hippocampus

  • Ilgam eKhalilov,
  • Ilgam eKhalilov,
  • Ilgam eKhalilov,
  • Geneviève eChazal,
  • Geneviève eChazal,
  • Geneviève eChazal,
  • Ilona eChudotvorova,
  • Ilona eChudotvorova,
  • Ilona eChudotvorova,
  • Christophe ePellegrino,
  • Christophe ePellegrino,
  • Christophe ePellegrino,
  • Severine eCorby,
  • Severine eCorby,
  • Severine eCorby,
  • Nadine eFerrand,
  • Nadine eFerrand,
  • Nadine eFerrand,
  • Olena eGubkina,
  • Olena eGubkina,
  • Olena eGubkina,
  • Romain eNardou,
  • Romain eNardou,
  • Romain eNardou,
  • Roman eTyzio,
  • Roman eTyzio,
  • Roman eTyzio,
  • Sumii eYamamoto,
  • Sumii eYamamoto,
  • Sumii eYamamoto,
  • Thomas J Jentsch,
  • Christian eHubner,
  • Jean-Luc eGaiarsa,
  • Jean-Luc eGaiarsa,
  • Jean-Luc eGaiarsa,
  • Yehezkel eBen-Ari,
  • Yehezkel eBen-Ari,
  • Yehezkel eBen-Ari,
  • Igor eMedina,
  • Igor eMedina,
  • Igor eMedina

DOI
https://doi.org/10.3389/fncel.2011.00023
Journal volume & issue
Vol. 5

Abstract

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The neuronal potassium-chloride co-transporter Kcc2 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 GABAergic postsynaptic currents (PSCs) than naïve age matched neurons. However, intracellular chloride concentration ([Cl-]i) and the reversal potential of GABA-mediated currents (EGABA) were similar in embryonic Kcc2+/+ and Kcc2-/- CA3 neurons. In addition, Kcc2 immuno-labelling 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 GABAergic 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 synapses formation and networks construction.

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