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KCC2-Mediated Cl- Extrusion Modulates Spontaneous Hippocampal Network Events in Perinatal Rats and Mice.


ABSTRACT: It is generally thought that hippocampal neurons of perinatal rats and mice lack transport-functional K-Cl cotransporter KCC2, and that Cl- regulation is dominated by Cl- uptake via the Na-K-2Cl cotransporter NKCC1. Here, we demonstrate a robust enhancement of spontaneous hippocampal network events (giant depolarizing potentials [GDPs]) by the KCC2 inhibitor VU0463271 in neonatal rats and late-gestation, wild-type mouse embryos, but not in their KCC2-null littermates. VU0463271 increased the depolarizing GABAergic synaptic drive onto neonatal CA3 pyramidal neurons, increasing their spiking probability and synchrony during the rising phase of a GDP. Our data indicate that Cl- extrusion by KCC2 is involved in modulation of GDPs already at their developmental onset during the perinatal period in mice and rats.

SUBMITTER: Spoljaric I 

PROVIDER: S-EPMC6352714 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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KCC2-Mediated Cl<sup>-</sup> Extrusion Modulates Spontaneous Hippocampal Network Events in Perinatal Rats and Mice.

Spoljaric Inkeri I   Spoljaric Albert A   Mavrovic Martina M   Seja Patricia P   Puskarjov Martin M   Kaila Kai K  

Cell reports 20190101 5


It is generally thought that hippocampal neurons of perinatal rats and mice lack transport-functional K-Cl cotransporter KCC2, and that Cl<sup>-</sup> regulation is dominated by Cl<sup>-</sup> uptake via the Na-K-2Cl cotransporter NKCC1. Here, we demonstrate a robust enhancement of spontaneous hippocampal network events (giant depolarizing potentials [GDPs]) by the KCC2 inhibitor VU0463271 in neonatal rats and late-gestation, wild-type mouse embryos, but not in their KCC2-null littermates. VU046  ...[more]

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