Spontaneous Network Events Driven by Depolarizing GABA Action in Neonatal Hippocampal Slices are Not Attributable to Deficient Mitochondrial Energy Metabolism

Ruusuvuori, Eva; Kirilkin, Ilya; Pandya, Nikhil J.; Kaila, Kai

doi:10.1523/jneurosci.3355-10.2010

Cited by 68 publications

(80 citation statements)

References 29 publications

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“…Moreover, the E GABA of the MNCs recorded in the energy-enriched medium (Ϫ34.5 Ϯ 2.7 mV, n ϭ 22) was essentially the same as that of the cells recorded in the ACSF (Ϫ34.0 Ϯ 1.6 mV, n ϭ 25). These results argue against the idea that the GABAergic excitation in the MNCs is an artifact of the metabolic conditions and fit with recent studies on GABAergic excitation in developing neurons (Kirmse et al, 2010;Ruusuvuori et al, 2010;Tyzio et al, 2011).…”

Section: Additional Control Experimentssupporting

confidence: 76%

Chronic Hyperosmotic Stress Converts GABAergic Inhibition into Excitation in Vasopressin and Oxytocin Neurons in the Rat

Kim¹,

Kim²,

Kim³

et al. 2011

J. Neurosci.

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In mammals, the increased secretion of arginine-vasopressin (AVP) (antidiuretic hormone) and oxytocin (natriuretic hormone) is a key physiological response to hyperosmotic stress. In this study, we examined whether chronic hyperosmotic stress weakens GABA A receptor-mediated synaptic inhibition in rat hypothalamic magnocellular neurosecretory cells (MNCs) secreting these hormones. Gramicidin-perforated recordings of MNCs in acute hypothalamic slices prepared from control rats and ones subjected to the chronic hyperosmotic stress revealed that this challenge not only attenuated the GABAergic inhibition but actually converted it into excitation. The hyperosmotic stress caused a profound depolarizing shift in the reversal potential of GABAergic response (E GABA ) in MNCs. This E GABA shift was associated with increased expression of NaϪ cotransporter 1 (NKCC1) in MNCs and was blocked by the NKCC inhibitor bumetanide as well as by decreasing NKCC activity through a reduction of extracellular sodium. Blocking central oxytocin receptors during the hyperosmotic stress prevented the switch to GABAergic excitation. Finally, intravenous injection of the GABA A receptor antagonist bicuculline lowered the plasma levels of AVP and oxytocin in rats under the chronic hyperosmotic stress. We conclude that the GABAergic responses of MNCs switch between inhibition and excitation in response to physiological needs through the regulation of transmembrane Cl Ϫ gradients.

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Section: Additional Control Experimentssupporting

confidence: 76%

Chronic Hyperosmotic Stress Converts GABAergic Inhibition into Excitation in Vasopressin and Oxytocin Neurons in the Rat

Kim¹,

Kim²,

Kim³

et al. 2011

J. Neurosci.

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“…However, subsequent reports, e.g. based on physiological pyruvate concentrations (200 mM), clearly contradicted the argument of pathophysiological depolarizing effects in immature neurons and instead support the classical concept of a developmental switch (Ruusuvuori et al, 2010;Kirmse and Witte, 2010;Tyzio et al, 2011).…”

Section: Regulationmentioning

confidence: 93%

Chloride cotransporters, chloride homeostasis, and synaptic inhibition in the developing auditory system

et al. 2011

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“…Although criticism [26][27][28] concerning the concept of depolarizing GABA has been largely invalidated in recent years [29][30][31][32][33] , supportive evidence from the intact mammalian brain is still lacking. In favour of a depolarizing GABA action in nonmammalian species in vivo, iontophoretic application of GABA or glycine was found to evoke somatic Ca 2 þ transients (CaTs) in spinal neurons of zebrafish larvae 34 .…”

mentioning

confidence: 99%

GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo

et al. 2015

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A large body of evidence from in vitro studies suggests that GABA is depolarizing during early postnatal development. However, the mode of GABA action in the intact developing brain is unknown. Here we examine the in vivo effects of GABA in cells of the upper cortical plate using a combination of electrophysiological and Ca 2 þ -imaging techniques. We report that at postnatal days (P) 3-4, GABA depolarizes the majority of immature neurons in the occipital cortex of anaesthetized mice. At the same time, GABA does not efficiently activate voltage-gated Ca 2 þ channels and fails to induce action potential firing. Blocking GABA A receptors disinhibits spontaneous network activity, whereas allosteric activation of GABA A receptors has the opposite effect. In summary, our data provide evidence that in vivo GABA acts as a depolarizing neurotransmitter imposing an inhibitory control on network activity in the neonatal (P3-4) neocortex.

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Spontaneous Network Events Driven by Depolarizing GABA Action in Neonatal Hippocampal Slices are Not Attributable to Deficient Mitochondrial Energy Metabolism

Cited by 68 publications

References 29 publications

Chronic Hyperosmotic Stress Converts GABAergic Inhibition into Excitation in Vasopressin and Oxytocin Neurons in the Rat

Chronic Hyperosmotic Stress Converts GABAergic Inhibition into Excitation in Vasopressin and Oxytocin Neurons in the Rat

Chloride cotransporters, chloride homeostasis, and synaptic inhibition in the developing auditory system

GABA depolarizes immature neurons and inhibits network activity in the neonatal neocortex in vivo

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