RT Journal Article
SR Electronic
T1 Compensatory Enhancement of Intrinsic Spiking upon NKCC1 Disruption in Neonatal Hippocampus
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 6982
OP 6988
DO 10.1523/JNEUROSCI.0443-09.2009
VO 29
IS 21
A1 Sampsa T. Sipilä
A1 Kristiina Huttu
A1 Junko Yamada
A1 Ramil Afzalov
A1 Juha Voipio
A1 Peter Blaesse
A1 Kai Kaila
YR 2009
UL http://www.jneurosci.org/content/29/21/6982.abstract
AB Depolarizing and excitatory GABA actions are thought to be important in cortical development. We show here that GABA has no excitatory action on CA3 pyramidal neurons in hippocampal slices from neonatal NKCC1−/− mice that lack the Na–K–2Cl cotransporter isoform 1. Strikingly, NKCC1−/− slices generated endogenous network events similar to giant depolarizing potentials (GDPs), but, unlike in wild-type slices, the GDPs were not facilitated by the GABAA agonist isoguvacine or blocked by the NKCC1 inhibitor bumetanide. The developmental upregulation of the K–Cl cotransporter 2 (KCC2) was unperturbed, whereas the pharmacologically isolated glutamatergic network activity and the intrinsic excitability of CA3 pyramidal neurons were enhanced in the NKCC1−/− hippocampus. Hence, developmental expression of KCC2, unsilencing of AMPA-type synapses, and early network events can take place in the absence of excitatory GABAergic signaling in the neonatal hippocampus. Furthermore, we show that genetic as well as pharmacologically induced loss of NKCC1-dependent excitatory actions of GABA results in a dramatic compensatory increase in the intrinsic excitability of glutamatergic neurons, pointing to powerful homeostatic regulation of neuronal activity in the developing hippocampal circuitry.