Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after Stroke

Summary: Ischemic stroke enhances the proliferation of adult-generated precursor cells that ectopically migrate toward the infarct. Studies have correlated precursor cell proliferation and subsequent adult neurogenesis with enhanced stroke recovery, yet it remains unclear whether stroke can generate...

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Main Authors: Timal S. Kannangara, Anthony Carter, Yingben Xue, Jagroop S. Dhaliwal, Jean-Claude Béïque, Diane C. Lagace
Format: Article
Language:English
Published: Elsevier 2018-12-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S221367111830434X
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author Timal S. Kannangara
Anthony Carter
Yingben Xue
Jagroop S. Dhaliwal
Jean-Claude Béïque
Diane C. Lagace
author_facet Timal S. Kannangara
Anthony Carter
Yingben Xue
Jagroop S. Dhaliwal
Jean-Claude Béïque
Diane C. Lagace
author_sort Timal S. Kannangara
collection DOAJ
description Summary: Ischemic stroke enhances the proliferation of adult-generated precursor cells that ectopically migrate toward the infarct. Studies have correlated precursor cell proliferation and subsequent adult neurogenesis with enhanced stroke recovery, yet it remains unclear whether stroke can generate new neurons capable of functional integration into the injured cortex. Here, using single and bitransgenic reporter mice, we identify spatial and temporal features of a multilineage cellular response to focal ischemia. We reveal that a small population of stroke-induced immature neurons accumulate within the peri-infarct region of the adult sensorimotor cortex, exhibit voltage-dependent conductances, fire action potentials, express GABAergic markers, and receive sparse GABAergic synaptic inputs. Collectively, these findings reveal that GABAergic neurons arising from the lateral ventricle have the capacity to integrate into the stroke-injured cortex, although their limited number and exiguous synaptic integration may limit their ability to participate in stroke recovery. : In this article, Kannangara and colleagues histologically and electrophysiologically characterized the precursor cell response evoked in the adult cortex after focal ischemia. The authors identify a population of doublecortin-expressing GABAergic immature neurons localized to the injured cortical regions with the capacity to fire action potentials and receive GABAergic input, indicative of functionally integration into the cortical network. Keywords: stroke, neurogenesis, GABA, cortex, ischemia, injury, photothrombosis, stem cells, brain repair, subventricular zone
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spelling doaj.art-c73212abef8c4d01b37b01d54a696e562022-12-22T01:47:03ZengElsevierStem Cell Reports2213-67112018-12-0111613271336Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after StrokeTimal S. Kannangara0Anthony Carter1Yingben Xue2Jagroop S. Dhaliwal3Jean-Claude Béïque4Diane C. Lagace5Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; University of Ottawa Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada; Neuroscience Program, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON K1G 5Z3, CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON K1G 5Z3, CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; University of Ottawa Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada; Neuroscience Program, University of Ottawa, Ottawa, ON K1H 8M5, CanadaDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; University of Ottawa Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada; Neuroscience Program, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON K1G 5Z3, Canada; Corresponding authorDepartment of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ottawa, ON K1H 8M5, Canada; University of Ottawa Brain and Mind Research Institute, Ottawa, ON K1H 8M5, Canada; Neuroscience Program, University of Ottawa, Ottawa, ON K1H 8M5, Canada; Canadian Partnership for Stroke Recovery, Ottawa, ON K1G 5Z3, Canada; Corresponding authorSummary: Ischemic stroke enhances the proliferation of adult-generated precursor cells that ectopically migrate toward the infarct. Studies have correlated precursor cell proliferation and subsequent adult neurogenesis with enhanced stroke recovery, yet it remains unclear whether stroke can generate new neurons capable of functional integration into the injured cortex. Here, using single and bitransgenic reporter mice, we identify spatial and temporal features of a multilineage cellular response to focal ischemia. We reveal that a small population of stroke-induced immature neurons accumulate within the peri-infarct region of the adult sensorimotor cortex, exhibit voltage-dependent conductances, fire action potentials, express GABAergic markers, and receive sparse GABAergic synaptic inputs. Collectively, these findings reveal that GABAergic neurons arising from the lateral ventricle have the capacity to integrate into the stroke-injured cortex, although their limited number and exiguous synaptic integration may limit their ability to participate in stroke recovery. : In this article, Kannangara and colleagues histologically and electrophysiologically characterized the precursor cell response evoked in the adult cortex after focal ischemia. The authors identify a population of doublecortin-expressing GABAergic immature neurons localized to the injured cortical regions with the capacity to fire action potentials and receive GABAergic input, indicative of functionally integration into the cortical network. Keywords: stroke, neurogenesis, GABA, cortex, ischemia, injury, photothrombosis, stem cells, brain repair, subventricular zonehttp://www.sciencedirect.com/science/article/pii/S221367111830434X
spellingShingle Timal S. Kannangara
Anthony Carter
Yingben Xue
Jagroop S. Dhaliwal
Jean-Claude Béïque
Diane C. Lagace
Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after Stroke
Stem Cell Reports
title Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after Stroke
title_full Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after Stroke
title_fullStr Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after Stroke
title_full_unstemmed Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after Stroke
title_short Excitable Adult-Generated GABAergic Neurons Acquire Functional Innervation in the Cortex after Stroke
title_sort excitable adult generated gabaergic neurons acquire functional innervation in the cortex after stroke
url http://www.sciencedirect.com/science/article/pii/S221367111830434X
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