title: NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain.
abstract: From an early postnatal period and throughout life there is a continuous production of olfactory bulb (OB) interneurons originating from neuronal precursors in the subventricular zone. To reach the OB circuits, immature neuroblasts migrate along the rostral migratory stream (RMS). In the present study, we employed cultured postnatal mouse forebrain slices and used lentiviral vectors to label neuronal precursors with GFP and to manipulate the expression levels of the Na-K-2Cl cotransporter NKCC1. We investigated the role of this Cl- transporter in different stages of postnatal neurogenesis, including neuroblast migration and integration in the OB networks once they have reached the granule cell layer (GCL). We report that NKCC1 activity is necessary for maintaining normal migratory speed. Both pharmacological and genetic manipulations revealed that NKCC1 maintains high [Cl-]i and regulates the resting membrane potential of migratory neuroblasts whilst its functional expression is strongly reduced at the time cells reach the GCL. As in other developing systems, NKCC1 shapes GABAA-dependent signaling in the RMS neuroblasts. Also, we show that NKCC1 controls the migration of neuroblasts in the RMS. The present study indeed indicates that the latter effect results from a novel action of NKCC1 on the resting membrane potential, which is independent of GABAA-dependent signaling. All in all, our findings show that early stages of the postnatal recruitment of OB interneurons rely on precise, orchestrated mechanisms that depend on multiple actions of NKCC1.
authors.affiliation: Institut Pasteur, Laboratory for Perception and Memory, Paris, France. mejiashe@univ-paris5.fr
authors.forename: Sheyla
authors.initials: S
authors.lastname: Mejia-Gervacio
authors.forename: Kerren
authors.initials: K
authors.lastname: Murray
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Lledo
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002465:Cell Movement / Q000235:genetics; D002478:Cells, Cultured; D000089622:Doublecortin Domain Proteins; D018682:GABA Agents / Q000494:pharmacology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D008564:Membrane Potentials / Q000187:drug effects / Q000235:genetics; D051379:Mice; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D058953:Neural Stem Cells / Q000502:physiology*; D009479:Neuropeptides / Q000378:metabolism; D009830:Olfactory Bulb / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D009924:Organ Culture Techniques; D018408:Patch-Clamp Techniques; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D016548:Prosencephalon / Q000166:cytology* / Q000254:growth & development*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D028021:Sodium-Potassium-Chloride Symporters / Q000235:genetics / Q000378:metabolism*; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters / Q000378:metabolism; D013997:Time Factors; D014162:Transfection / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*; D000096922:K Cl- Cotransporters
chemical_list: D000089622:Doublecortin Domain Proteins; D018682:GABA Agents; D049452:Green Fluorescent Proteins; D008869:Microtubule-Associated Proteins; D009479:Neuropeptides; D010751:Phosphopyruvate Hydratase; D034741:RNA, Small Interfering; D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D027981:Symporters; D005680:gamma-Aminobutyric Acid; D000096922:K Cl- Cotransporters; C578878:Slc12a2 protein, mouse