Excitatory actions of GABA during development
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1
INMED-INSERM U901, France
Early in development, GABA exerts depolarizing and excitatory actions on immature neurons and contributes, in synergy with glutamate, to generation of the primitive network activity pattern of Giant Depolarizing Potentials (GDPs). Depolarizing action of GABA is due to elevated intracellular chloride concentration set by chloride co-transporter NKCC1. GABA only slightly depolarizes postsynaptic cells and GABA reversal potential barely attends action potential threshold. Postsynaptic excitation by GABA requires activation of voltage-gated persistent sodium channels which amplify GABA responses, at cost of long and variable delay in spike-to-spike transmission at GABAergic synapses. Long delays at GABAergic synapses determine asynchronous population firing during GDPs and slow GDP’s propagation.
Depolarizing action of GABA is not simply linked to the cell age, but it is also modulated by hormones. During delivery, excitatory action of GABA is suppressed by oxytocin, essential hormone for labor. This likely involves a blockade of NKCC1 activity that causes reduction in intracellular chloride concentration. As maintenance of depolarizing GABA consumes energy, loss of depolarizing GABA saves energy during delivery. As a result, immature neurons become more resistant to ischemic insult. Another benefit from oxytocin-mediated excitatory-to-inhibitory switch in the action of GABA consists in alleviation of fetal pain during delivery.
Conference:
EMBO workshop: Gaba Signalling and Brain Networks , Amsterdam, Netherlands, 30 Jun - 2 Jul, 2010.
Presentation Type:
Oral Presentation
Topic:
Talks
Citation:
Khazipov
R
(2010). Excitatory actions of GABA during development.
Conference Abstract:
EMBO workshop: Gaba Signalling and Brain Networks .
doi: 10.3389/conf.fnins.2010.15.00037
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Received:
23 Jun 2010;
Published Online:
23 Jun 2010.
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Correspondence:
Rustem Khazipov, INMED-INSERM U901, Marseille, France, roustem.khazipov@inserm.fr