Transient Cell-intrinsic Activity Regulates the Migration and Laminar Positioning of Cortical Projection Neurons

Article Article scientifique Article Transient Cell-intrinsic Activity Regulates the Migration and Laminar Positioning of Cortical Projection Neurons eng 2017 author Hurni Nicolas 734392 author Kolodziejczak Marta 845354 author Tomasello Ugo 835285 author Badia Cabre Joan 852472 author Jacobshagen Moritz 736320 author Prados Julien 0000-0002-8546-241X 561771 author Dayer Alexandre 84495 3052-3063 10.1093/cercor/bhx059 28334356 1047-3211 Neocortical microcircuits are built during development and require the coordinated assembly of excitatory glutamatergic projection neurons (PNs) into functional networks. Neuronal migration is an essential step in this process. In addition to cell-intrinsic mechanisms, external cues including neurotransmitters regulate cortical neuron migration, suggesting that early activity could influence this process. Here, we aimed to investigate the role of cell-intrinsic activity in migrating PNs in vivo using a designer receptor exclusively activated by a designer drug (DREADD) chemogenetic approach. In utero electroporation was used to specifically express the human M3 muscarinic cholinergic Gq-coupled receptor (hM3Dq) in PNs and calcium activity, migratory dynamics, gene expression, and laminar positioning of PNs were assessed following embryonic DREADD activation. We found that transient embryonic DREADD activation induced premature branching and transcriptional changes in migrating PNs leading to a persistent laminar mispositioning of superficial layer PNs into deep cortical layers without affecting expression of layer-specific molecular identity markers. In addition, live imaging approaches indicated that embryonic DREADD activation increased calcium transients in migrating PNs and altered their migratory dynamics by increasing their pausing time. Taken together, these results support the idea that increased cell-intrinsic activity during migration acts as a stop signal for migrating cortical PNs. Dewey 616 Dewey 616.89 54 Département de microbiologie et médecine moléculaire 21B 60 Département de psychiatrie 225 false 535 Groupe Dayer Alexandre (Formation du circuit cortical) 875 Cerebral Cortex 27 5 12762358-8d07-4042-aa0a-4e645e313156 Article (Published version) Public Hurni_CerebCortex_2017.pdf 2333761 application/pdf openAccess Faculté de médecine / Section de médecine fondamentale / Département de microbiologie et médecine moléculaire Faculté de médecine / Section de médecine clinique / Département de psychiatrie

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Transient Cell-intrinsic Activity Regulates the Migration and Laminar Positioning of Cortical Projection Neurons	Cerebral Cortex			2017	534	388

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Kolodziejczak, Marta