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J Physiol Volume 559, Number 1, 129-139, August 15, 2004 DOI: 10.1113/jphysiol.2004.065060
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Spontaneous synaptic activity is required for the formation of functional GABAergic synapses in the developing rat hippocampus

Isabelle Colin-Le Brun, Nadine Ferrand, Olivier Caillard, Patrizia Tosetti, Yehezkel Ben-Ari and Jean-Luc Gaïarsa

Institut de Neurobiologie de la Mediterranée (INMED), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 29, BP 13, 13273 Marseille Cedex 09, France

Here we examine the role of the spontaneous synaptic activity generated by the developing rat hippocampus in the formation of functional {gamma}-aminobutyric acid (GABA) synapses. Intact hippocampal formations (IHFs) were dissected at birth and incubated for 1 day in control or tetrodotoxin (TTX)-supplemented medium at 25°C. After the incubation, miniature GABAA-mediated postsynaptic currents (mGABAA-PSCs) were recorded in whole-cell voltage-clamped CA3 pyramidal neurones from IHF-derived slices. After 1 day in vitro in control medium, the frequency of mGABAA-PSCs was similar to that recorded in acute slices obtained 1 day after birth, but significantly higher than the frequency recorded from acute slices just after birth. These results suggest that the factors required in vivo for the formation of functional GABAergic synapses are preserved in the IHFs in vitro. The frequency increase was prevented when IHFs were incubated for 1 day with TTX. TTX treatment affected neither the morphology of CA3 pyramidal neurones nor cell viability. The TTX effects were reproduced when IHFs were incubated in the presence of glutamatergic or GABAergic ionotropic receptor antagonists or in high divalent cationic medium. The present results indicate that the spontaneous synaptic activity generated by the developing hippocampus is a key player in the formation of functional GABAergic synapses, possibly via network events requiring both glutamatergic and GABAergic receptors.

(Received 22 March 2004; accepted after revision 15 June 2004; first published online 24 June 2004)
Corresponding author J.-L. Gaïarsa: Institut de Neurobiologie de la Mediterranée (INMED), Institut National de la Santé et de la Recherche Médicale (INSERM), Unité 29, BP 13, 13273 Marseille Cedex 09, France. Email: gaiarsa{at}inmed.univ-mrs.fr




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