Early Development of Neuronal Activity in the Primate HippocampusIn 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.

SLC25A12 expression is associated with neurite outgrowth and is upregulated in the prefrontal cortex of autistic subjects

“…The hippocampus matures postnatally in rodents, whereas it develops prenatally in primates. [38][39][40] We observed Slc25a12 expression in postnatal mouse hippocampus (P21), whereas the Slc25a12 transcript was not detected in the 23 weeks human hippocampus (Supplementary Figure S5b), consistent with the relative developmental periods. In addition, no molecular gradient of Slc25a12 expression was observed in the mouse brain.…”

Neuronal Differentiation in the Adult Hippocampus Recapitulates Embryonic Development

“…The slow kinetics of GABAergic PSCs suggests a dendritic localization of the early GABAergic connections (see Discussion) (Miles et al, 1996;Banks et al, 1998Banks et al, , 2002). These findings demonstrate that GABAergic interneurons are the primary source of synaptic inputs onto immature neurons in the adult hippocampus, similar to what occurs to CA1 pyramidal neurons and DGCs during development (Tyzio et al, 1999;Khazipov et al, 2001;Gozlan and Ben Ari, 2003).…”

Choosing the Correct Antiepileptic Drugs: From Animal Studies to the Clinic

“…This is due to the higher input resistance of immature neurons that facilitate the generation of action potentials and enhance excitability. In addition, during the early postnatal period, at a time when the immature brain is highly susceptible to seizures [15,16], GABA exerts paradoxical excitatory action in all animal species and brain structures including primate in utero suggesting that this rule has been preserved throughout evolution [17]. Immature neurons are enriched with a high intracellular concentration of chloride leading to an efflux of chloride instead of an influx when GABA receptors are activated [18,19].…”