Early-life serotonin dysregulation affects the migration and positioning of cortical interneuron subtypes

Article Article scientifique Article Early-life serotonin dysregulation affects the migration and positioning of cortical interneuron subtypes eng 2015 author Frazer Sarah Louise 738392 author Otomo Kanako 776180 author Dayer Alexandre 84495 e644 10.1038/tp.2015.147 26393490 2158-3188 Early-life deficiency of the serotonin transporter (SERT) gives rise to a wide range of psychiatric-relevant phenotypes; however, the molecular and cellular targets of serotonin dyregulation during neural circuit formation remain to be identified. Interestingly, migrating cortical interneurons (INs) derived from the caudal ganglionic eminence (CGE) have been shown to be more responsive to serotonin-mediated signalling compared with INs derived from the medial ganglionic eminence (MGE). Here we investigated the impact of early-life SERT deficiency on the migration and positioning of CGE-derived cortical INs in SERT-ko mice and in mice exposed to the SERT inhibitor fluoxetine during the late embryonic period. Using confocal time-lapse imaging and microarray-based expression analysis we found that genetic and pharmacological SERT deficiency significantly increased the migratory speed of CGE-derived INs and affected transcriptional programmes regulating neuronal migration. Postnatal studies revealed that SERT deficiency altered the cortical laminar distribution of subtypes of CGE-derived INs but not MGE-derived INs. More specifically, we found that the distribution of vasointestinal peptide (VIP)-expressing INs in layer 2/3 was abnormal in both genetic and pharmacological SERT-deficiency models. Collectively, these data indicate that early-life SERT deficiency has an impact on the migration and molecular programmes of CGE-derived INs, thus leading to specific alterations in the positioning of VIP-expressing INs. These data add to the growing evidence that early-life serotonin dysregulation affects cortical microcircuit formation and contributes to the emergence of psychiatric-relevant phenotypes. Dewey 616.8 Dewey 616.89 53 Département de neurosciences fondamentales 21A 60 Département de psychiatrie 225 false 535 Groupe Dayer Alexandre (Formation du circuit cortical) 875 Translational psychiatry 5 3923d8e0-c7b1-4d2c-8cf9-56d0ba91ad3c Article (Published version) Public Dayer_TranslPsychiatry_2015.pdf 4251712 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de neurosciences fondamentales Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Early-life serotonin dysregulation affects the migration and positioning of cortical interneuron subtypes	Translational psychiatry			2015	535	286

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Otomo, Kanako