<i>Dlx5/6</i> 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, <i>Dlx5</i> and <i>Dlx6</i> (<i>Dlx5/6</i>) genes are involved in...
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MDPI AG
2022-05-01
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| author | Rym Aouci Mey El Soudany Zakaria Maakoul Anastasia Fontaine Hiroki Kurihara Giovanni Levi Nicolas Narboux-Nême |
| author_facet | Rym Aouci Mey El Soudany Zakaria Maakoul Anastasia Fontaine Hiroki Kurihara Giovanni Levi Nicolas Narboux-Nême |
| author_sort | Rym Aouci |
| collection | DOAJ |
| description | Neuronal circuits integrating Parvalbumin-positive GABAergic inhibitory interneurons (PV) are essential for normal brain function and are often altered in psychiatric conditions. During development, <i>Dlx5</i> and <i>Dlx6</i> (<i>Dlx5/6</i>) genes are involved in the differentiation of PV-interneurons. In the adult, <i>Dlx5/6</i> 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 <i>Dlx5/6</i> in mouse GABAergic neurons (<i>Dlx5/6<sup>VgatCre</sup></i> mice) results in altered behavioural and metabolic profiles. Here we evaluate the consequences of targeted <i>Dlx5/6</i> gene dosage alterations in adult GABAergic neurons. We compare the effects on normal brain of homozygous and heterozygous (<i>Dlx5/6<sup>VgatCre</sup></i> and <i>Dlx5/6<sup>VgatCre/+</sup></i> mice) <i>Dlx5/6</i> deletions to those of <i>Dlx5</i> targeted overexpression (<i>GABAergic<sup>Dlx5/+</sup></i> mice). We find a linear correlation between <i>Dlx5/6</i> allelic dosage and the density of PV-positive neurons in the adult prelimbic cortex and in the hippocampus. In parallel, we observe that <i>Dlx5/6</i> 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 <i>Dlx5/6</i> expression is involved in individual cognitive variability and, possibly, in the genesis of certain neuropsychiatric conditions. |
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| last_indexed | 2024-03-10T01:25:51Z |
| publishDate | 2022-05-01 |
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| spelling | doaj.art-649875d716fa4237b5a34d63c2db5e662023-11-23T13:52:02ZengMDPI AGCells2073-44092022-05-011111173910.3390/cells11111739<i>Dlx5/6</i> Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive BehavioursRym Aouci0Mey El Soudany1Zakaria Maakoul2Anastasia Fontaine3Hiroki Kurihara4Giovanni Levi5Nicolas Narboux-Nême6Physiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d’Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, FrancePhysiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d’Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, FrancePhysiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d’Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, FrancePhysiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d’Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, FranceDepartment of Physiological Chemistry and Metabolism, Graduate School of Medicine, The University of Tokyo, Tokyo 113-0033, JapanPhysiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d’Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, FrancePhysiologie Moléculaire et Adaptation, CNRS UMR7221, Team BBC, Département AVIV, Muséum National d’Histoire Naturelle, UMR-7221, 7 rue Cuvier, 75005 Paris, FranceNeuronal circuits integrating Parvalbumin-positive GABAergic inhibitory interneurons (PV) are essential for normal brain function and are often altered in psychiatric conditions. During development, <i>Dlx5</i> and <i>Dlx6</i> (<i>Dlx5/6</i>) genes are involved in the differentiation of PV-interneurons. In the adult, <i>Dlx5/6</i> 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 <i>Dlx5/6</i> in mouse GABAergic neurons (<i>Dlx5/6<sup>VgatCre</sup></i> mice) results in altered behavioural and metabolic profiles. Here we evaluate the consequences of targeted <i>Dlx5/6</i> gene dosage alterations in adult GABAergic neurons. We compare the effects on normal brain of homozygous and heterozygous (<i>Dlx5/6<sup>VgatCre</sup></i> and <i>Dlx5/6<sup>VgatCre/+</sup></i> mice) <i>Dlx5/6</i> deletions to those of <i>Dlx5</i> targeted overexpression (<i>GABAergic<sup>Dlx5/+</sup></i> mice). We find a linear correlation between <i>Dlx5/6</i> allelic dosage and the density of PV-positive neurons in the adult prelimbic cortex and in the hippocampus. In parallel, we observe that <i>Dlx5/6</i> 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 <i>Dlx5/6</i> expression is involved in individual cognitive variability and, possibly, in the genesis of certain neuropsychiatric conditions.https://www.mdpi.com/2073-4409/11/11/1739GABAergic neurons<i>DLX5/6</i> genesparvalbuminbehaviourgene regulationautism |
| spellingShingle | Rym Aouci Mey El Soudany Zakaria Maakoul Anastasia Fontaine Hiroki Kurihara Giovanni Levi Nicolas Narboux-Nême <i>Dlx5/6</i> Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours Cells GABAergic neurons <i>DLX5/6</i> genes parvalbumin behaviour gene regulation autism |
| title | <i>Dlx5/6</i> Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours |
| title_full | <i>Dlx5/6</i> Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours |
| title_fullStr | <i>Dlx5/6</i> Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours |
| title_full_unstemmed | <i>Dlx5/6</i> Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours |
| title_short | <i>Dlx5/6</i> Expression Levels in Mouse GABAergic Neurons Regulate Adult Parvalbumin Neuronal Density and Anxiety/Compulsive Behaviours |
| title_sort | i dlx5 6 i expression levels in mouse gabaergic neurons regulate adult parvalbumin neuronal density and anxiety compulsive behaviours |
| topic | GABAergic neurons <i>DLX5/6</i> genes parvalbumin behaviour gene regulation autism |
| url | https://www.mdpi.com/2073-4409/11/11/1739 |
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