Publicação
Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus
| 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. |
|---|---|
| Autores principais: | Campbell, Nolan R. |
| Outros Autores: | Fernandes, Catarina C.; Halff, Andrew W.; Berg, Darwin K. |
| Assunto: | Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
| Ano: | 2010 |
| País: | Portugal |
| Tipo de documento: | artigo |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| _version_ | 1866809569751072768 |
|---|---|
| author | Campbell, Nolan R. |
| author2 | Fernandes, Catarina C. Halff, Andrew W. Berg, Darwin K. |
| author2_role | author author author |
| author_facet | Campbell, Nolan R. Fernandes, Catarina C. Halff, Andrew W. Berg, Darwin K. |
| author_role | author |
| contributor_name_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| country_str | PT |
| creators_json_txt | [{\"Person.name\":\"Campbell, Nolan R.\"},{\"Person.name\":\"Fernandes, Catarina C.\"},{\"Person.name\":\"Halff, Andrew W.\"},{\"Person.name\":\"Berg, Darwin K.\"}] |
| datacite.contributors.contributor.contributorName.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| datacite.creators.creator.creatorName.fl_str_mv | Campbell, Nolan R. Fernandes, Catarina C. Halff, Andrew W. Berg, Darwin K. |
| datacite.date.Accepted.fl_str_mv | 2010-01-01T00:00:00Z |
| datacite.date.available.fl_str_mv | 2012-05-03T15:16:40Z |
| datacite.date.embargoed.fl_str_mv | 2012-05-03T15:16:40Z |
| datacite.rights.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| datacite.subjects.subject.fl_str_mv | Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
| datacite.titles.title.fl_str_mv | Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
| dc.contributor.none.fl_str_mv | Repositório Científico de Acesso Aberto da ULisboa |
| dc.creator.none.fl_str_mv | Campbell, Nolan R. Fernandes, Catarina C. Halff, Andrew W. Berg, Darwin K. |
| dc.date.Accepted.fl_str_mv | 2010-01-01T00:00:00Z |
| dc.date.available.fl_str_mv | 2012-05-03T15:16:40Z |
| dc.date.embargoed.fl_str_mv | 2012-05-03T15:16:40Z |
| dc.format.none.fl_str_mv | application/pdf |
| dc.identifier.none.fl_str_mv | http://hdl.handle.net/10451/6205 |
| dc.language.none.fl_str_mv | eng |
| dc.publisher.none.fl_str_mv | Society for Neuroscience |
| dc.rights.none.fl_str_mv | http://purl.org/coar/access_right/c_abf2 |
| dc.subject.none.fl_str_mv | Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
| dc.title.fl_str_mv | Endogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampus |
| dc.type.none.fl_str_mv | http://purl.org/coar/resource_type/c_6501 |
| 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. |
| dirty | 0 |
| eu_rights_str_mv | openAccess |
| format | article |
| fulltext.url.fl_str_mv | https://repositorio.ulisboa.pt/bitstreams/c256e104-9ea3-4f2c-9fd8-3aee4a75daa3/download |
| id | ul_a3b2bbca53940dd6c6138f116a7efa94 |
| identifier.url.fl_str_mv | http://hdl.handle.net/10451/6205 |
| instacron_str | ul |
| institution | Universidade de Lisboa |
| instname_str | Universidade de Lisboa |
| language | eng |
| network_acronym_str | ul |
| network_name_str | Repositório da Universidade de Lisboa |
| oai_identifier_str | oai:repositorio.ulisboa.pt:10451/6205 |
| organization_str_mv | urn:organizationAcronym:ul |
| person_str_mv | Campbell, Nolan R. Fernandes, Catarina C. Halff, Andrew W. Berg, Darwin K. |
| publishDate | 2010 |
| publisher.none.fl_str_mv | Society for Neuroscience |
| reponame_str | Repositório da Universidade de Lisboa |
| repository_id_str | urn:repositoryAcronym:ul |
| service_str_mv | urn:repositoryAcronym:ul |
| spelling | engSociety for NeuroscienceengNeurogenesis 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.application/pdfengEndogenous signaling through α7-containing nicotinic receptors promotes maturation and integration of adult-born neurons in the hippocampusCampbell, Nolan R.Fernandes, Catarina C.Halff, Andrew W.Berg, Darwin K.HostingInstitutionOrganizationalRepositório Científico de Acesso Aberto da ULisboae-mailmailto:repositorio@reitoria.ulisboa.ptrepositorio@reitoria.ulisboa.ptURLhttp://www.jneurosci.org/content/30/26/8734.full.pdf+htmlN/ADOI:10.1523/JNEUROSCI.0931-10.2010ISSNIsPartOf0270-64742012-05-03T15:16:40Z20102010-01-01T00:00:00ZHandlehttp://hdl.handle.net/10451/6205http://purl.org/coar/access_right/c_abf2open accessNeurogenesisAdultHippocampusReceptors, nicotinicMaturation-promoting factorNeurons1995002 bytesliteraturehttp://purl.org/coar/resource_type/c_6501journal articlehttp://purl.org/coar/access_right/c_abf2application/pdffulltexthttps://repositorio.ulisboa.pt/bitstreams/c256e104-9ea3-4f2c-9fd8-3aee4a75daa3/downloadJournal of Neuroscience87348744 |
| 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 |
| status | SINGLETON |
| subject.fl_str_mv | Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
| title | 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_short | 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 |
| topic | Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
| topic_facet | Neurogenesis Adult Hippocampus Receptors, nicotinic Maturation-promoting factor Neurons |
| url | http://hdl.handle.net/10451/6205 |
| visible | 1 |