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Received March 22, 2004
Revised April 19, 2004
Accepted after revision June 15, 2004
1 INSERM U29/INMED
* To whom correspondence should be addressed. E-mail: gaiarsa{at}inmed.univ-mrs.fr.
Here we examine the role of the spontaneous synaptic activity generated by the developing rat hippocampus in the formation of functional g-aminobutyric acid (GABA) synapses. Intact hippocampal formations (IHFs) were dissected at birth and incubated for one day in control or tetrodotoxin (TTX) supplemented medium at room temperature. After the incubation, miniature GABAA-mediated postsynaptic currents (mGABAA-PSCs) were recorded in whole-cell voltage-clamped CA3 pyramidal neurons from IHF-derived slices. After one day in vitro in control medium, the frequency of mGABAA-PSCs was similar to that recorded in acute slices obtained one 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 one day with TTX. TTX-treatment affected neither the morphology of CA3 pyramidal neurons 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.
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