Journal
CELL REPORTS
Volume 26, Issue 5, Pages 1073-+Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2019.01.011
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Funding
- Academy of Finland
- European Research Council [ERC-2013-AdG 341116]
- Emil Aaltonen Foundation [0000-0003-0668-5955]
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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, wildtype 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.
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