Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.
Maternal Oxytocin Triggers a Transient Inhibitory Switch in GABA Signaling in the Fetal Brain During Delivery
Roman Tyzio,1
Rosa Cossart,1
Ilgam Khalilov,1
Marat Minlebaev,1
Christian A. Hübner,2
Alfonso Represa,1
Yehezkel Ben-Ari,1*
Rustem Khazipov1
Abstract:
We report a signaling mechanism in rats between mother and fetusaimed at preparing fetal neurons for delivery. In immature neurons,-aminobutyric acid (GABA) is the primary excitatory neurotransmitter.We found that, shortly before delivery, there is a transientreduction in the intracellular chloride concentration and anexcitatory-to-inhibitory switch of GABA actions. These eventswere triggered by oxytocin, an essential maternal hormone forlabor. In vivo administration of an oxytocin receptor antagonistbefore delivery prevented the switch of GABA actions in fetalneurons and aggravated the severity of anoxic episodes. Thus,maternal oxytocin inhibits fetal neurons and increases theirresistance to insults during delivery.
1 Institut de Neurobiologie de la Méditerranée, INSERM U29, Université de la Méditerranée, Campus Scientifique de Luminy, Boite Postale 13, 13273 Marseille Cedex 09, France. 2 Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, 20251 Hamburg, Germany.
* To whom correspondence should be addressed. E-mail: ben-ari{at}inmed.univ-mrs.fr
The editors suggest the following Related Resources on Science sites:
In Science Magazine
TECHNICAL COMMENTS
Lionel Carbillon (13 July 2007) Science317 (5835), 197a.
[DOI: 10.1126/science.1141090] |Abstract »|Full Text »|PDF »
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The Synchronization within and Interaction between the Default and Dorsal Attention Networks in Early Infancy.
W. Gao, J. H. Gilmore, D. Shen, J. K. Smith, H. Zhu, and W. Lin (2013)
Cereb Cortex
23, 594-603
|Abstract »|Full Text »|PDF »
Oxytocin Promotes Long-Term Potentiation by Enhancing Epidermal Growth Factor Receptor-Mediated Local Translation of Protein Kinase M{zeta}.
The GABA Excitatory/Inhibitory Shift in Brain Maturation and Neurological Disorders.
Y. Ben-Ari, I. Khalilov, K. T. Kahle, and E. Cherubini (2012)
Neuroscientist
18, 467-486
|Abstract »|Full Text »|PDF »
Oxytocin Inhibits the Membrane Depolarization-Induced Increase in Intracellular Calcium in Capsaicin Sensitive Sensory Neurons: A Peripheral Mechanism of Analgesic Action.
S. Hobo, K.-i. Hayashida, and J. C. Eisenach (2012)
Anesth. Analg.
114, 442-449
|Abstract »|Full Text »|PDF »
Review Article: Neurotoxicity of Anesthetic Drugs in the Developing Brain.
Upregulation of KCC2 Activity by Zinc-Mediated Neurotransmission via the mZnR/GPR39 Receptor.
E. Chorin, O. Vinograd, I. Fleidervish, D. Gilad, S. Herrmann, I. Sekler, E. Aizenman, and M. Hershfinkel (2011)
J. Neurosci.
31, 12916-12926
|Abstract »|Full Text »|PDF »
Depolarizing Actions of GABA in Immature Neurons Depend Neither on Ketone Bodies Nor on Pyruvate.
R. Tyzio, C. Allene, R. Nardou, M. A. Picardo, S. Yamamoto, S. Sivakumaran, M. D. Caiati, S. Rheims, M. Minlebaev, M. Milh, et al. (2011)
J. Neurosci.
31, 34-45
|Abstract »|Full Text »|PDF »
Progressive NKCC1-Dependent Neuronal Chloride Accumulation during Neonatal Seizures.
V. I. Dzhala, K. V. Kuchibhotla, J. C. Glykys, K. T. Kahle, W. B. Swiercz, G. Feng, T. Kuner, G. J. Augustine, B. J. Bacskai, and K. J. Staley (2010)
J. Neurosci.
30, 11745-11761
|Abstract »|Full Text »|PDF »
How GABA generates depolarization.
N. C. Spitzer (2010)
J. Physiol.
588, 757-758
|Full Text »|PDF »
Downregulation of Potassium Chloride Cotransporter KCC2 After Transient Focal Cerebral Ischemia.
Compensatory Enhancement of Intrinsic Spiking upon NKCC1 Disruption in Neonatal Hippocampus.
S. T. Sipila, K. Huttu, J. Yamada, R. Afzalov, J. Voipio, P. Blaesse, and K. Kaila (2009)
J. Neurosci.
29, 6982-6988
|Abstract »|Full Text »|PDF »
Differential contribution of the Na+-K+-2Cl- cotransporter NKCC1 to chloride handling in rat embryonic dorsal root ganglion neurons and motor neurons.
J. N. Chabwine, K. Talavera, L. Verbert, J. Eggermont, J.-M. Vanderwinden, H. De Smedt, L. Van Den Bosch, W. Robberecht, and G. Callewaert (2009)
FASEB J
23, 1168-1176
|Abstract »|Full Text »|PDF »
Sequential Generation of Two Distinct Synapse-Driven Network Patterns in Developing Neocortex.
C. Allene, A. Cattani, J. B. Ackman, P. Bonifazi, L. Aniksztejn, Y. Ben-Ari, and R. Cossart (2008)
J. Neurosci.
28, 12851-12863
|Abstract »|Full Text »|PDF »
Monitoring of chloride and activity of glycine receptor channels using genetically encoded fluorescent sensors.
M. Mukhtarov, O. Markova, E. Real, Y. Jacob, S. Buldakova, and P. Bregestovski (2008)
Phil Trans R Soc A
366, 3445-3462
|Abstract »|Full Text »|PDF »
Development of input connections in neural cultures.
J. Soriano, M. Rodriguez Martinez, T. Tlusty, and E. Moses (2008)
PNAS
105, 13758-13763
|Abstract »|Full Text »|PDF »
Excitatory GABA in Rodent Developing Neocortex In Vitro.
S. Rheims, M. Minlebaev, A. Ivanov, A. Represa, R. Khazipov, G. L. Holmes, Y. Ben-Ari, and Y. Zilberter (2008)
J Neurophysiol
100, 609-619
|Abstract »|Full Text »|PDF »
Layer-Specific Generation and Propagation of Seizures in Slices of Developing Neocortex: Role of Excitatory GABAergic Synapses.
S. Rheims, A. Represa, Y. Ben-Ari, and Y. Zilberter (2008)
J Neurophysiol
100, 620-628
|Abstract »|Full Text »|PDF »
Timing of Neonatal Seizures and Intrapartum Obstetrical Factors.
M. S. Scher, D. A. Steppe, and M. Beggarly (2008)
J Child Neurol
23, 640-643
|Abstract »|PDF »
Central and peripheral neuroimmune responses: hyporesponsiveness during pregnancy.
S. J. Spencer, A. Mouihate, M. A. Galic, and Q. J. Pittman (2008)
J. Physiol.
586, 399-406
|Abstract »|Full Text »|PDF »
Generation of Slow Network Oscillations in the Developing Rat Hippocampus After Blockade of Glutamate Uptake.
A. A. Cattani, V. D. Bonfardin, A. Represa, Y. Ben-Ari, and L. Aniksztejn (2007)
J Neurophysiol
98, 2324-2336
|Abstract »|Full Text »|PDF »
GABA: A Pioneer Transmitter That Excites Immature Neurons and Generates Primitive Oscillations.
Y. Ben-Ari, J.-L. Gaiarsa, R. Tyzio, and R. Khazipov (2007)
Physiol Rev
87, 1215-1284
|Abstract »|Full Text »|PDF »
Comment on "Maternal Oxytocin Triggers a Transient Inhibitory Switch in GABA Signaling in the Fetal Brain During Delivery".
-aminobutyric acid (GABA) is the primary excitatory neurotransmitter. We found that, shortly before delivery, there is a transient reduction in the intracellular chloride concentration and an excitatory-to-inhibitory switch of GABA actions. These events were triggered by oxytocin, an essential maternal hormone for labor. In vivo administration of an oxytocin receptor antagonist before delivery prevented the switch of GABA actions in fetal neurons and aggravated the severity of anoxic episodes. Thus, maternal oxytocin inhibits fetal neurons and increases their resistance to insults during delivery. 
