Biphasic impact of prenatal inflammation and macrophage depletion on the wiring of neocortical inhibitory circuits

Morgane Sonia Thion (1) , Coralie-Anne Mosser (2) , Isabelle Ferezou (3) , Pauline Grisel (1) , Sofia Baptista (2) , Donovan Low (4) , Florent Ginhoux (5) , Sonia Garel (6) , Etienne Audinat (2, 7)

1 IBENS - Institut de biologie de l'ENS Paris
2 U1128 - Laboratoire de Neurophysiologie et Nouvelles Microscopies
3 NeuroPSI - Institut des Neurosciences Paris-Saclay
4 SIgN - Singapore Immunology Network
5 A*STAR - Agency for science, technology and research [Singapore]
6 Génétique moléculaire du développement
7 IGF - Institut de Génomique Fonctionnelle

The etiology of neurodevelopmental disorders is linked to defects in parvalbumin (PV)-expressing cortical interneurons and to prenatal immune challenges. Mouse models of maternal immune activation (MIA) and microglia deficits increase the postnatal density of PV interneurons, raising the question of their functional integration. Here, we show that MIA and embryonic depletion of macrophages including microglia have a two-step impact on PV interneurons wiring onto their excitatory target neurons in the barrel cortex. In adults, both challenges reduced the inhibitory drive from PV interneurons, as reported in neurodevelopmental disorders. In juveniles, however, we found an increased density of PV neurons, an enhanced strength of unitary connections onto excitatory cells, and an aberrant horizontal inhibition with a reduced lateral propagation of sensory inputs in vivo. Our results provide a comprehensive framework for understanding the impact of prenatal immune challenges onto the developmental trajectory of inhibitory circuits that leads to pathological brain wiring.

Domaines: Neurosciences [q-bio.NC]

Morgane Sonia Thion, Coralie-Anne Mosser, Isabelle Ferezou, Pauline Grisel, Sofia Baptista, et al.. Biphasic impact of prenatal inflammation and macrophage depletion on the wiring of neocortical inhibitory circuits. Cell Reports, 2019, 28 (5), pp.1119-1126.e4. ⟨10.1016/j.celrep.2019.06.086⟩. ⟨hal-02335984⟩