Compensatory enhancement of intrinsic spiking upon NKCC1 disruption in neonatal hippocampus

Sampsa T. Sipila, Kristiina Huttu, Junko Yamada, Ramil Afzalov, Juha Voipio, Peter Blaesse, Kai Kaila

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

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.
Alkuperäiskielienglanti
LehtiJournal of Neuroscience
Vuosikerta29
Numero21
Sivut6982-6988
Sivumäärä7
ISSN0270-6474
DOI - pysyväislinkit
TilaJulkaistu - 2009
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 311 Peruslääketieteet
  • 318 Lääketieteen bioteknologia
  • 411 Maatalous ja metsätieteet
  • 118 Biotieteet
  • 219 Ympäristön bioteknologia
  • 519 Yhteiskuntamaantiede, talousmaantiede
  • 515 Psykologia

Lainaa tätä

Sipila, Sampsa T. ; Huttu, Kristiina ; Yamada, Junko ; Afzalov, Ramil ; Voipio, Juha ; Blaesse, Peter ; Kaila, Kai. / Compensatory enhancement of intrinsic spiking upon NKCC1 disruption in neonatal hippocampus. Julkaisussa: Journal of Neuroscience. 2009 ; Vuosikerta 29, Nro 21. Sivut 6982-6988.
@article{b7838355d28948cbad597830eae485eb,
title = "Compensatory enhancement of intrinsic spiking upon NKCC1 disruption in neonatal hippocampus",
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.",
keywords = "GIANT DEPOLARIZING POTENTIALS, DEVELOPING RAT HIPPOCAMPUS, NEOCORTICAL NEURONS, PYRAMIDAL NEURONS, AMPA RECEPTORS, GABA, COTRANSPORTER, KCC2, EXPRESSION, BRAIN, 311 Basic medicine, 318 Medical biotechnology, 411 Agriculture and forestry, 118 Biological sciences, 219 Environmental biotechnology, 519 Social and economic geography, 515 Psychology",
author = "Sipila, {Sampsa T.} and Kristiina Huttu and Junko Yamada and Ramil Afzalov and Juha Voipio and Peter Blaesse and Kai Kaila",
year = "2009",
doi = "10.1523/JNEUROSCI.0443-09.2009",
language = "English",
volume = "29",
pages = "6982--6988",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society of Neuroscience",
number = "21",

}

Compensatory enhancement of intrinsic spiking upon NKCC1 disruption in neonatal hippocampus. / Sipila, Sampsa T.; Huttu, Kristiina; Yamada, Junko; Afzalov, Ramil; Voipio, Juha; Blaesse, Peter; Kaila, Kai.

julkaisussa: Journal of Neuroscience, Vuosikerta 29, Nro 21, 2009, s. 6982-6988.

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

TY - JOUR

T1 - Compensatory enhancement of intrinsic spiking upon NKCC1 disruption in neonatal hippocampus

AU - Sipila, Sampsa T.

AU - Huttu, Kristiina

AU - Yamada, Junko

AU - Afzalov, Ramil

AU - Voipio, Juha

AU - Blaesse, Peter

AU - Kaila, Kai

PY - 2009

Y1 - 2009

N2 - 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.

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 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.

KW - GIANT DEPOLARIZING POTENTIALS

KW - DEVELOPING RAT HIPPOCAMPUS

KW - NEOCORTICAL NEURONS

KW - PYRAMIDAL NEURONS

KW - AMPA RECEPTORS

KW - GABA

KW - COTRANSPORTER

KW - KCC2

KW - EXPRESSION

KW - BRAIN

KW - 311 Basic medicine

KW - 318 Medical biotechnology

KW - 411 Agriculture and forestry

KW - 118 Biological sciences

KW - 219 Environmental biotechnology

KW - 519 Social and economic geography

KW - 515 Psychology

U2 - 10.1523/JNEUROSCI.0443-09.2009

DO - 10.1523/JNEUROSCI.0443-09.2009

M3 - Article

VL - 29

SP - 6982

EP - 6988

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 21

ER -