Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours.

Neuronal circuits integrating Parvalbumin-positive GABAergic inhibitory interneurons (PV) are essential for normal brain function and are often altered in psychiatric conditions. During development, and () genes are involved in the differentiation of PV-interneurons. In the adult, continue to be expressed at low levels in most telencephalic GABAergic neurons, but their importance in determining the number and distribution of adult PV-interneurons is unknown. Previously, we have shown that targeted deletion of in mouse GABAergic neurons ( mice) results in altered behavioural and metabolic profiles. Here we evaluate the consequences of targeted gene dosage alterations in adult GABAergic neurons. We compare the effects on normal brain of homozygous and heterozygous ( and mice) deletions to those of targeted overexpression ( mice). We find a linear correlation between allelic dosage and the density of PV-positive neurons in the adult prelimbic cortex and in the hippocampus. In parallel, we observe that expression levels in GABAergic neurons are also linearly associated with the intensity of anxiety and compulsivity-like behaviours. Our findings reinforce the notion that regulation of expression is involved in individual cognitive variability and, possibly, in the genesis of certain neuropsychiatric conditions.