La construction synaptique in-utero

d'après le travail de

Khazipov R, Esclapez M, Caillard O, Bernard C, Khalilov I, Tyzio R, Hirsch J, Dzhala V, Berger B, Ben-Ari Y.

Vers la moitié de la gestation, le cerveau de primate est immature. Aucune synapse n'est fonctionnelle. Telle est l'une des conclusions du travail de Yehezekiel Ben- Ari (Unité Inserm 29), basé sur un enregistrement de l'activité neuronale in utero chez le macaque, jamais réalisé jusqu'ici (The journal of neuroscience, 2001, 21-24, 9770-9781). En revanche, une semaine avant la naissance, les neurones sont très développés avec près de 7000 synapses (10 000 synapses chez l'adulte). Donc en moins de deux mois, le cerveau est capable de passer d'un stade relativement silencieux à un stade relativement mature. De plus les premières synapses apparaissant vers la moitié de la gestation sont gabaergiques Conséquences en extrapolant à l'homme : les précautions avec les benzodiazépines, qui agissent sur ce type de récepteurs, doivent surtout être renforcées lors de la deuxième moitié de la grossesse.

Sources

• Institut de Neurobiologie de la Mediterranee/Institut National de la Sante et de la Recherche Medicale (INSERM) U29, Luminy, 13273 Marseille, France.
• à écouter
• à lire :Early development of neuronal activity in the primate hippocampus in utero, Khazipov R, Esclapez M, Caillard O, Bernard C, Khalilov I, Tyzio R, Hirsch J, Dzhala V, Berger B, Ben-Ari Y., J Neurosci 2001 Dec 15;21(24):9770-81

Abstract

of "Early development of neuronal activity in the primate hippocampus in utero, Khazipov R, Esclapez M, Caillard O, Bernard C, Khalilov I, Tyzio R, Hirsch J, Dzhala V, Berger B, Ben-Ari Y., J Neurosci 2001 Dec 15;21(24):9770-81"

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.

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