title: Early development of neuronal activity in the primate hippocampus in utero.
abstract: Morphological studies suggest that the primate hippocampus develops extensively before birth, but little is known about its functional development. Patch-clamp recordings of hippocampal neurons and reconstruction of biocytin-filled pyramidal cells were performed in slices of macaque cynomolgus fetuses delivered by cesarean section. We found that during the second half of gestation, axons and dendrites of pyramidal cells grow intensively by hundreds of micrometers per day to attain a high level of maturity near term. Synaptic currents appear around midgestation and are correlated with the level of morphological differentiation of pyramidal cells: the first synapses are GABAergic, and their emergence correlates with the growth of apical dendrite into stratum radiatum. A later occurrence of glutamatergic synaptic currents correlates with a further differentiation of the axodendritic tree and the appearance of spines. Relying on the number of dendritic spines, we estimated that hundreds of new glutamatergic synapses are established every day on a pyramidal neuron during the last third of gestation. Most of the synaptic activity is synchronized in spontaneous slow ( approximately 0.1 Hz) network oscillations reminiscent of the giant depolarizing potentials in neonatal rodents. Epileptiform discharges can be evoked by the GABA(A) receptor antagonist bicuculline by the last third of gestation, and postsynaptic GABA(B) receptors contribute to the termination of epileptiform discharges. Comparing the results obtained in primates and rodents, we conclude that the template of early hippocampal network development is conserved across the mammalian evolution but that it is shifted toward fetal life in primate.
authors.affiliation: Institut de Neurobiologie de la Méditerranée/Institut National de la Santé et de la Recherche Médicale (INSERM) U29, Luminy, 13273 Marseille, France. khazipov@inmed.univ-mrs.fr
authors.forename: R
authors.initials: R
authors.lastname: Khazipov
authors.forename: M
authors.initials: M
authors.lastname: Esclapez
authors.forename: O
authors.initials: O
authors.lastname: Caillard
authors.forename: C
authors.initials: C
authors.lastname: Bernard
authors.forename: I
authors.initials: I
authors.lastname: Khalilov
authors.forename: R
authors.initials: R
authors.lastname: Tyzio
authors.forename: J
authors.initials: J
authors.lastname: Hirsch
authors.forename: V
authors.initials: V
authors.lastname: Dzhala
authors.forename: B
authors.initials: B
authors.lastname: Berger
authors.forename: Y
authors.initials: Y
authors.lastname: Ben-Ari
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology; D001683:Biological Clocks / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D003712:Dendrites / Q000502:physiology; D004827:Epilepsy / Q000139:chemically induced / Q000503:physiopathology; D018756:GABA Antagonists / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D006624:Hippocampus / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D066298:In Vitro Techniques; D007395:Interneurons / Q000502:physiology / Q000648:ultrastructure; D008239:Lysine / Q000031:analogs & derivatives*; D008252:Macaca fascicularis; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009415:Nerve Net / Q000187:drug effects / Q000196:embryology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D017966:Pyramidal Cells / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
chemical_list: D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D005680:gamma-Aminobutyric Acid; C013411:biocytin; D008239:Lysine