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NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain

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 stu...

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Autores principales: Mejia-Gervacio, Sheyla, Murray, Kerren, Lledo, Pierre-Marie
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038882/
https://www.ncbi.nlm.nih.gov/pubmed/21284844
http://dx.doi.org/10.1186/1749-8104-6-4
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author Mejia-Gervacio, Sheyla
Murray, Kerren
Lledo, Pierre-Marie
author_facet Mejia-Gervacio, Sheyla
Murray, Kerren
Lledo, Pierre-Marie
author_sort Mejia-Gervacio, Sheyla
collection PubMed
description 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 GABA(A)-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 GABA(A)-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.
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spelling pubmed-30388822011-02-15 NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain Mejia-Gervacio, Sheyla Murray, Kerren Lledo, Pierre-Marie Neural Dev Research Article 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 GABA(A)-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 GABA(A)-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. BioMed Central 2011-02-01 /pmc/articles/PMC3038882/ /pubmed/21284844 http://dx.doi.org/10.1186/1749-8104-6-4 Text en Copyright ©2011 Mejia-Gervacio et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mejia-Gervacio, Sheyla
Murray, Kerren
Lledo, Pierre-Marie
NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain
title NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain
title_full NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain
title_fullStr NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain
title_full_unstemmed NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain
title_short NKCC1 controls GABAergic signaling and neuroblast migration in the postnatal forebrain
title_sort nkcc1 controls gabaergic signaling and neuroblast migration in the postnatal forebrain
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038882/
https://www.ncbi.nlm.nih.gov/pubmed/21284844
http://dx.doi.org/10.1186/1749-8104-6-4
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