Impaired bidirectional communication between interneurons and oligodendrocyte precursor cells affects social cognitive behavior

Abstract

Cortical neural circuits are complex but very precise networks of balanced excitation and inhibition. Yet, the molecular and cellular mechanisms that form the balance are just beginning to emerge. Here, using conditional γ-aminobutyric acid receptor B1- deficient mice we identify a γ-aminobutyric acid/tumor necrosis factor superfamily member 12-mediated bidirectional communication pathway between parvalbumin-positive fast spiking interneurons and oligodendrocyte precursor cells that determines the density and function of interneurons in the developing medial prefrontal cortex. Interruption of the GABAergic signaling to oligodendrocyte precursor cells results in reduced myelination and hypoactivity of interneurons, strong changes of cortical network activities and impaired social cognitive behavior. In conclusion, glial transmitter receptors are pivotal elements in finetuning distinct brain functions.

Early postnatal interruption of the bidirectional GABA/TNFSF12 signaling between parvalbumin-positive interneurons and oligodendrocyte precursor cells impairs correct prefrontal cortical network activity and social cognitive behavior later in life.