Dlx5/6 involvement in the postnatal maturation of cortical parvalbumin neurons during critical periods

Brain activity depends on GABAergic inhibitory interneurons. Dlx5 and Dlx6 are two closely related homeobox genes, expressed by the telencephalic ganglionic eminences. In the adult brain, Dlx5/6 are expressed in most cortical GABAergic interneurons.In the prefrontal cortex, Parvalbumin-positive neurons (PV-neurons) are involved in cognitive functions, and their maturation is critical for cognitive development. Using mouse lines in which Dlx5/6 are either invalidated or overexpressed in GABAergic neurons, we have recently shown that the adult density of PV-neurons is directly correlated to Dlx5/6 expression levels and that variations in Dlx5/6 expression affect adult anxiety and compulsive behaviours.In addition, PV-neurons play a crucial role in the postnatal maturation of the cerebral cortex, in the mouse. They are required for the progression a fundamental maturation process: the cortical critical periods (CPs). During the CPs, PV-neurons undergo sequential steps in their maturation: first the expression of Parvalbumin is activated, then the enwrapment of the cell bodies by the peri-neuronal net (PNN) a specialized extracellular matrix.Here we show that Dlx5/6 expression is required for the maturation of PV-neurons during the CPs affecting both Parvalbumin expression of and the formation of the PNN. Both the invalidation and the overexpression of Dlx5/6 impact these two critical steps of cortical maturation by inducing distinct region-specific alterations in PV-neurons density and causing PNN localized disorganization.We conclude that Dlx5/6 are involved in the genetic cascade controlling cortical maturation and CPs timing and might play a role in the adaptation to the environment during the postnatal period.