Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus
Autor(a) principal: | |
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Data de Publicação: | 2010 |
Outros Autores: | , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
Texto Completo: | http://hdl.handle.net/10451/6205 |
Resumo: | Neurogenesis in the dentate gyrus occurs throughout adult mammalian life and is essential for proper hippocampal function. Early in their development, adult-born neurons express homomeric α7-containing nicotinic acetylcholine receptors (α7-nAChRs) and receive direct cholinergic innervation. We show here that functional α7-nAChRs are necessary for normal survival, maturation, and integration of adult-born neurons in the dentate gyrus. Stereotaxic retroviral injection into the dentate gyrus of wild-type and α7-knock-out (α7KO) male and female mice was used to label and birthdate adult-born neurons for morphological and electrophysiological measures; BrdU (5-bromo-2-deoxyuridine) injections were used to quantify cell survival. In α7KO mice, we find that adult-born neurons develop with truncated, less complex dendritic arbors and display GABAergic postsynaptic currents with immature kinetics. The neurons also have a prolonged period of GABAergic depolarization characteristic of an immature state. In this condition, they receive fewer spontaneous synaptic currents and are more prone to die during the critical period when adult-born neurons are normally integrated into behaviorally relevant networks. Even those adult-born neurons that survive the critical period retain long-term dendritic abnormalities in α7KO mice. Interestingly, local infection with retroviral constructs to knockdown α7-mRNA mimics the α7KO phenotype, demonstrating that the relevant α7-nAChR signaling is cell autonomous. The results indicate a profound role for α7-nAChRs in adult neurogenesis and predict that α7-nAChR loss will cause progressive impairment in hippocampal circuitry and function over time as fewer neurons are added to the dentate gyrus and those that are added integrate less well. |
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Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampusNeurogenesisAdultHippocampusReceptors, nicotinicMaturation-promoting factorNeuronsNeurogenesis in the dentate gyrus occurs throughout adult mammalian life and is essential for proper hippocampal function. Early in their development, adult-born neurons express homomeric α7-containing nicotinic acetylcholine receptors (α7-nAChRs) and receive direct cholinergic innervation. We show here that functional α7-nAChRs are necessary for normal survival, maturation, and integration of adult-born neurons in the dentate gyrus. Stereotaxic retroviral injection into the dentate gyrus of wild-type and α7-knock-out (α7KO) male and female mice was used to label and birthdate adult-born neurons for morphological and electrophysiological measures; BrdU (5-bromo-2-deoxyuridine) injections were used to quantify cell survival. In α7KO mice, we find that adult-born neurons develop with truncated, less complex dendritic arbors and display GABAergic postsynaptic currents with immature kinetics. The neurons also have a prolonged period of GABAergic depolarization characteristic of an immature state. In this condition, they receive fewer spontaneous synaptic currents and are more prone to die during the critical period when adult-born neurons are normally integrated into behaviorally relevant networks. Even those adult-born neurons that survive the critical period retain long-term dendritic abnormalities in α7KO mice. Interestingly, local infection with retroviral constructs to knockdown α7-mRNA mimics the α7KO phenotype, demonstrating that the relevant α7-nAChR signaling is cell autonomous. The results indicate a profound role for α7-nAChRs in adult neurogenesis and predict that α7-nAChR loss will cause progressive impairment in hippocampal circuitry and function over time as fewer neurons are added to the dentate gyrus and those that are added integrate less well.This work was supported by National Institutes of Health Grants NS012601 and N0S35469, and the Tobacco-Related Disease Research Program (16RT-0167). N.R.C. is a Tobacco-Related Disease Research Program predoctoral fellow. C.C.F. is a Fundação Calouste Gulbenkian Graduate Fellow. A.W.F. is a National Research Service Award predoctoral fellow. We thank Gouping Feng (Duke University, Durham, NC) for the GFP-reporter mouse line and Xiao-Yun Wang for expert technical assistance.Society for NeuroscienceRepositório da Universidade de LisboaCampbell, Nolan R.Fernandes, Catarina C.Halff, Andrew W.Berg, Darwin K.2012-05-03T15:16:40Z20102010-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/6205engThe Journal of Neuroscience, June 30, 2010 • 30(26):8734–87440270-6474info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T15:48:34Zoai:repositorio.ul.pt:10451/6205Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:31:23.464625Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
dc.title.none.fl_str_mv |
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
title |
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
spellingShingle |
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus Campbell, Nolan R. Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
title_short |
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
title_full |
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
title_fullStr |
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
title_full_unstemmed |
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
title_sort |
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
author |
Campbell, Nolan R. |
author_facet |
Campbell, Nolan R. Fernandes, Catarina C. Halff, Andrew W. Berg, Darwin K. |
author_role |
author |
author2 |
Fernandes, Catarina C. Halff, Andrew W. Berg, Darwin K. |
author2_role |
author author author |
dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
dc.contributor.author.fl_str_mv |
Campbell, Nolan R. Fernandes, Catarina C. Halff, Andrew W. Berg, Darwin K. |
dc.subject.por.fl_str_mv |
Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
topic |
Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
description |
Neurogenesis in the dentate gyrus occurs throughout adult mammalian life and is essential for proper hippocampal function. Early in their development, adult-born neurons express homomeric α7-containing nicotinic acetylcholine receptors (α7-nAChRs) and receive direct cholinergic innervation. We show here that functional α7-nAChRs are necessary for normal survival, maturation, and integration of adult-born neurons in the dentate gyrus. Stereotaxic retroviral injection into the dentate gyrus of wild-type and α7-knock-out (α7KO) male and female mice was used to label and birthdate adult-born neurons for morphological and electrophysiological measures; BrdU (5-bromo-2-deoxyuridine) injections were used to quantify cell survival. In α7KO mice, we find that adult-born neurons develop with truncated, less complex dendritic arbors and display GABAergic postsynaptic currents with immature kinetics. The neurons also have a prolonged period of GABAergic depolarization characteristic of an immature state. In this condition, they receive fewer spontaneous synaptic currents and are more prone to die during the critical period when adult-born neurons are normally integrated into behaviorally relevant networks. Even those adult-born neurons that survive the critical period retain long-term dendritic abnormalities in α7KO mice. Interestingly, local infection with retroviral constructs to knockdown α7-mRNA mimics the α7KO phenotype, demonstrating that the relevant α7-nAChR signaling is cell autonomous. The results indicate a profound role for α7-nAChRs in adult neurogenesis and predict that α7-nAChR loss will cause progressive impairment in hippocampal circuitry and function over time as fewer neurons are added to the dentate gyrus and those that are added integrate less well. |
publishDate |
2010 |
dc.date.none.fl_str_mv |
2010 2010-01-01T00:00:00Z 2012-05-03T15:16:40Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/6205 |
url |
http://hdl.handle.net/10451/6205 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
The Journal of Neuroscience, June 30, 2010 • 30(26):8734–8744 0270-6474 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
application/pdf |
dc.publisher.none.fl_str_mv |
Society for Neuroscience |
publisher.none.fl_str_mv |
Society for Neuroscience |
dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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