| Title | Compensatory enhancement of intrinsic spiking upon NKCC1 disruption in neonatal hippocampus. | | Author(s) | Sipilä ST, Huttu K, Yamada J, Afzalov R, Voipio J, Blaesse P, Kaila K | | Institution | Department of Clinical Neurophysiology, Oulu University Hospital, FI-90230 Oulu, Finland. | | Source | J Neurosci 2009 May 27; 29(21):6982-8. | | MeSH | Action Potentials
Age Factors
Animals
Animals, Newborn
Benzodiazepines
Biophysics
Calcium
Electric Stimulation
Excitatory Amino Acid Antagonists
Excitatory Postsynaptic Potentials
Hippocampus
Mice
Mice, Knockout
Nerve Net
Patch-Clamp Techniques
Pyramidal Cells
Quinoxalines
Sodium-Potassium-Chloride Symporters
Symporters
Up-Regulation
gamma-Aminobutyric Acid
| | Abstract | 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 GABA(A) 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. | | Language | eng | | Pub Type(s) | In Vitro
Journal Article
Research Support, Non-U.S. Gov't
| | PubMed ID | 19474325 |
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