| Autor: |
Aouci R; Physiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d'Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, France., El Soudany M; Physiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d'Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, France., Maakoul Z; Physiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d'Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, France., Fontaine A; Physiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d'Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, France., Kurihara H; Department of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, Japan., Levi G; Physiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d'Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, France., Narboux-Nême N; Physiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d'Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, France. |
| Abstrakt: |
Neuronal circuits integrating Parvalbumin-positive GABAergic inhibitory interneurons (PV) are essential for normal brain function and are often altered in psychiatric conditions. During development, Dlx5 and Dlx6 ( Dlx5/6 ) genes are involved in the differentiation of PV-interneurons. In the adult, Dlx5/6 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 Dlx5/6 in mouse GABAergic neurons ( Dlx5/6 VgatCre mice) results in altered behavioural and metabolic profiles. Here we evaluate the consequences of targeted Dlx5/6 gene dosage alterations in adult GABAergic neurons. We compare the effects on normal brain of homozygous and heterozygous ( Dlx5/6 VgatCre and Dlx5/6 VgatCre/+ mice) Dlx5/6 deletions to those of Dlx5 targeted overexpression ( GABAergic Dlx5/+ mice). We find a linear correlation between Dlx5/6 allelic dosage and the density of PV-positive neurons in the adult prelimbic cortex and in the hippocampus. In parallel, we observe that Dlx5/6 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 Dlx5/6 expression is involved in individual cognitive variability and, possibly, in the genesis of certain neuropsychiatric conditions. |
