title: Spontaneous synaptic activity is required for the formation of functional GABAergic synapses in the developing rat hippocampus.
abstract: 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 degrees C. After the incubation, miniature GABA(A)-mediated postsynaptic currents (mGABA(A)-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 mGABA(A)-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.
authors.affiliation: 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.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Colin-Le Brun
authors.forename: Nadine
authors.initials: N
authors.lastname: Ferrand
authors.forename: Olivier
authors.initials: O
authors.lastname: Caillard
authors.forename: Patrizia
authors.initials: P
authors.lastname: Tosetti
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Ben-Ari
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Gaïarsa
mesh_terms: D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000187:drug effects / Q000254:growth & development*; D066298:In Vitro Techniques; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000502:physiology*; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000502:physiology
chemical_list: D018755:GABA Agonists; D018756:GABA Antagonists; D058785:GABA-A Receptor Agonists; D058787:GABA-A Receptor Antagonists; D011963:Receptors, GABA-A; D005680:gamma-Aminobutyric Acid