The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth

Amandine Fernandez , Camille Dumon , Damien Guimond , Roman Tyzio (1, 2) , Paolo Bonifazi (3) , Natalia Lozovaya , Nail Burnashev (2) , Diana C Ferrari , Yehezkel Ben-Ari (4, 2)

1 Epilepsie et ischémie cérébrale
2 INMED - INSERM U1249 - Institut de Neurobiologie de la Méditerranée [Aix-Marseille Université]
3 TAU - School of Physics and Astronomy [Tel Aviv]
4 Epilepsie et Ischemie Cerebrale

Epidemiological and experimental studies suggest that maternal immune activation (MIA) leads to developmental brain disorders, but whether the pathogenic mechanism impacts neurons already at birth is not known. We now report that MIA abolishes in mice the oxytocin-mediated delivery γ-aminobutyric acid (GABA) shift from depolarizing to hyperpolarizing in CA3 pyramidal neurons, and this is restored by the NKCC1 chloride importer antagonist bumetanide. Furthermore, MIA hippocampal pyramidal neurons at birth have a more exuberant apical arbor organization and increased apical dendritic length than age-matched controls. The frequency of spontaneous glutamatergic postsynaptic currents is also increased in MIA offspring, as well as the pairwise correlation of the synchronized firing of active cells in CA3. These alterations produced by MIA persist, since at P14-15 GABA action remains depolarizing, produces excitatory action, and network activity remains elevated with a higher frequency of spontaneous glutamatergic postsynaptic currents. Therefore, the pathogenic actions of MIA lead to important morphophysiological and network alterations in the hippocampus already at birth.

Mots clés: Excitatory-inhibitory imbalance; Apical arborization; Hippocampal network; Poly(I:C); Pyramidal neurons

Domaines: Neurosciences [q-bio.NC]

Amandine Fernandez, Camille Dumon, Damien Guimond, Roman Tyzio, Paolo Bonifazi, et al.. The GABA Developmental Shift Is Abolished by Maternal Immune Activation Already at Birth. Cerebral Cortex, 2018, pp.1 - 11. ⟨hal-01963851⟩