title: Early sequential formation of functional GABA(A) and glutamatergic synapses on CA1 interneurons of the rat foetal hippocampus.
abstract: During postnatal development of CA1 pyramidal neurons, GABAergic synapses are excitatory and established prior to glutamatergic synapses. As interneurons are generated before pyramidal cells, we have tested the hypothesis that the GABAergic interneuronal network is operative before glutamate pyramidal neurons and provides the initial patterns of activity. We patch-clamp recorded interneurons in foetal (69 neurons) and neonatal P0 (162 neurons) hippocampal slices and performed a morphofunctional analysis of biocytin-filled neurons. At P0, three types of interneurons were found: (i) non-innervated "silent" interneurons (5%) with no spontaneous or evoked synaptic currents; (ii) G interneurons (17%) with GABA(A) synapses only; and (iii) GG interneurons with GABA and glutamatergic synapses (78%). Relying on the neuronal capacitance, cell body size and arborization of dendrites and axons, the three types of interneurons correspond to three stages of development with non-innervated neurons and interneurons with GABA(A) and glutamatergic synapses being, respectively, the least and the most developed. Recordings from both pyramidal neurons and interneurons in foetuses (E18-20) revealed that the majority of interneurons (65%) had functional synapses whereas nearly 90% of pyramidal neurons were quiescent. Therefore, interneurons follow the same GABA-glutamate sequence of synapse formation but earlier than the principal cells. Interneurons are the source and the target of the first synapses formed in the hippocampus and are thus in a position to modulate the development of the hippocampus in the foetal stage.
authors.affiliation: INMED-INSERM Unité 29, Université de la Méditerranée, 163, route de Luminy, BP 13, 13273 Marseille cedex 9, France.
authors.forename: Sonia
authors.initials: S
authors.lastname: Hennou
authors.forename: Ilgam
authors.initials: I
authors.lastname: Khalilov
authors.forename: Diabé
authors.initials: D
authors.lastname: Diabira
authors.forename: Yehezkel
authors.initials: Y
authors.lastname: Ben-Ari
authors.forename: Henri
authors.initials: H
authors.lastname: Gozlan
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D048429:Cell Size / Q000502:physiology; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000502:physiology; D005260:Female; D005333:Fetus; D018698:Glutamic Acid / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D007150:Immunohistochemistry; D007395:Interneurons / Q000166:cytology / Q000378:metabolism*; D008239:Lysine / Q000031:analogs & derivatives*; D009434:Neural Pathways / Q000166:cytology / Q000196:embryology* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D011247:Pregnancy; D017966:Pyramidal Cells / Q000166:cytology / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011963:Receptors, GABA-A / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism* / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D011963:Receptors, GABA-A; D017470:Receptors, Glutamate; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; C013411:biocytin; D008239:Lysine