Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons

Many connections in the basal ganglia are made around birth when animals are exposed to a host of new affective, cognitive, and sensori-motor stimuli. It is thought that dopamine modulates cortico-striatal synapses that result in the strengthening of those connections that lead to desired outcomes....

Full description

Autores:
Tipo de recurso:
Fecha de publicación:
2012
Institución:
Universidad del Rosario
Repositorio:
Repositorio EdocUR - U. Rosario
Idioma:
eng
OAI Identifier:
oai:repository.urosario.edu.co:10336/8766
Acceso en línea:
http://repository.urosario.edu.co/handle/10336/8766
Palabra clave:
Enfermedades
Ganglios basales
dopamina
Neurología
Rights
License
Abierto (Texto completo)
id EDOCUR2_b47b1bd4c168eaaf008076ad3c334aec
oai_identifier_str oai:repository.urosario.edu.co:10336/8766
network_acronym_str EDOCUR2
network_name_str Repositorio EdocUR - U. Rosario
repository_id_str
dc.title.spa.fl_str_mv Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
title Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
spellingShingle Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
Enfermedades
Ganglios basales
dopamina
Neurología
title_short Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
title_full Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
title_fullStr Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
title_full_unstemmed Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
title_sort Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
dc.subject.ddc.none.fl_str_mv Enfermedades
topic Enfermedades
Ganglios basales
dopamina
Neurología
dc.subject.decs.spa.fl_str_mv Ganglios basales
dopamina
Neurología
description Many connections in the basal ganglia are made around birth when animals are exposed to a host of new affective, cognitive, and sensori-motor stimuli. It is thought that dopamine modulates cortico-striatal synapses that result in the strengthening of those connections that lead to desired outcomes. We propose that there must be a time before which stimuli cannot be processed into functional connections, otherwise it would imply an effective link between stimulus, response, and reward in uterus. Consistent with these ideas, we present evidence that early in development dopamine neurons are electrically immature and do not produce high-frequency firing in response to salient stimuli. We ask first, what makes dopamine neurons immature? and second, what are the implications of this immaturity for the basal ganglia? As an answer to the first question, we find that at birth the outward current is small (3nS-V), insensitive to Ca2z, TEA, BK, and SK blockers. Rapidly after birth, the outward current increases to 15nS-V and becomes sensitive to Ca2z, TEA, BK, and SK blockers. We make a detailed analysis of the kinetics of the components of the outward currents and produce a model for BK and SK channels that we use to reproduce the outward current, and to infer the geometrical arrangement of BK and Ca2z channels in clusters. In the first cluster, T-type Ca2z and BK channels are coupled within distances of *20 nm (200 A˚). The second cluster consists of L-type Ca2z and BK channels that are spread over distances of at least 60 nm. As for the second question, we propose that early in development, the mechanism of action selection is in a ‘‘locked-in’’ state that would prevent dopamine neurons from reinforcing cortico-striatal synapses that do not have a functional experiential- based value.
publishDate 2012
dc.date.created.none.fl_str_mv 2012-12
dc.date.issued.none.fl_str_mv 2012
dc.date.accessioned.none.fl_str_mv 2014-08-11T15:37:52Z
dc.date.available.none.fl_str_mv 2014-08-11T15:37:52Z
dc.type.eng.fl_str_mv article
dc.type.coar.fl_str_mv http://purl.org/coar/resource_type/c_6501
dc.type.spa.spa.fl_str_mv Artículo
dc.identifier.issn.none.fl_str_mv ISSN:1932-6203
dc.identifier.uri.none.fl_str_mv http://repository.urosario.edu.co/handle/10336/8766
identifier_str_mv ISSN:1932-6203
url http://repository.urosario.edu.co/handle/10336/8766
dc.language.iso.none.fl_str_mv eng
language eng
dc.relation.citationIssue.none.fl_str_mv No. 12
dc.relation.citationTitle.none.fl_str_mv PLOS ONE
dc.relation.citationVolume.none.fl_str_mv Vol. 7
dc.relation.ispartof.spa.fl_str_mv PLOS ONE, ISSN 1932-6203, V. 7 N. 12 Dec, 2012
dc.relation.uri.none.fl_str_mv http://www.ncbi.nlm.nih.gov.ez.urosario.edu.co/pmc/articles/PMC3527479/pdf/pone.0051610.pdf
dc.rights.coar.fl_str_mv http://purl.org/coar/access_right/c_abf2
dc.rights.acceso.spa.fl_str_mv Abierto (Texto completo)
rights_invalid_str_mv Abierto (Texto completo)
http://purl.org/coar/access_right/c_abf2
dc.format.medium.spa.fl_str_mv Recurso electrónico
dc.format.mimetype.none.fl_str_mv application/pdf
dc.format.tipo.spa.fl_str_mv Documento
dc.publisher.spa.fl_str_mv Universidad del Rosario
institution Universidad del Rosario
dc.source.instname.spa.fl_str_mv instname:Universidad del Rosario
dc.source.reponame.spa.fl_str_mv reponame:Repositorio Institucional EdocUR
bitstream.url.fl_str_mv https://repository.urosario.edu.co/bitstreams/8aabbfcd-9659-4f7a-9ed8-3c487dca833c/download
https://repository.urosario.edu.co/bitstreams/8a143232-1e2f-4d02-a39f-c79f4b64b027/download
https://repository.urosario.edu.co/bitstreams/871cc567-ba1e-4981-a62c-9b19bac02610/download
https://repository.urosario.edu.co/bitstreams/0e5b805e-a07b-4ac3-9f97-3a2de64f1535/download
bitstream.checksum.fl_str_mv e704113457d73ec61b9a53a62157275f
b4f8fe66e94b897ab4c355bac005ad16
8acfbfb923cbffe761f0f29e8da40d05
0637b360f9a3a510d4f9271e8ec73f33
bitstream.checksumAlgorithm.fl_str_mv MD5
MD5
MD5
MD5
repository.name.fl_str_mv Repositorio institucional EdocUR
repository.mail.fl_str_mv edocur@urosario.edu.co
_version_ 1814167735010066432
spelling Comunidad Rosarista6830d620-424a-4f8b-9d11-3e1f088777056002014-08-11T15:37:52Z2014-08-11T15:37:52Z2012-122012Many connections in the basal ganglia are made around birth when animals are exposed to a host of new affective, cognitive, and sensori-motor stimuli. It is thought that dopamine modulates cortico-striatal synapses that result in the strengthening of those connections that lead to desired outcomes. We propose that there must be a time before which stimuli cannot be processed into functional connections, otherwise it would imply an effective link between stimulus, response, and reward in uterus. Consistent with these ideas, we present evidence that early in development dopamine neurons are electrically immature and do not produce high-frequency firing in response to salient stimuli. We ask first, what makes dopamine neurons immature? and second, what are the implications of this immaturity for the basal ganglia? As an answer to the first question, we find that at birth the outward current is small (3nS-V), insensitive to Ca2z, TEA, BK, and SK blockers. Rapidly after birth, the outward current increases to 15nS-V and becomes sensitive to Ca2z, TEA, BK, and SK blockers. We make a detailed analysis of the kinetics of the components of the outward currents and produce a model for BK and SK channels that we use to reproduce the outward current, and to infer the geometrical arrangement of BK and Ca2z channels in clusters. In the first cluster, T-type Ca2z and BK channels are coupled within distances of *20 nm (200 A˚). The second cluster consists of L-type Ca2z and BK channels that are spread over distances of at least 60 nm. As for the second question, we propose that early in development, the mechanism of action selection is in a ‘‘locked-in’’ state that would prevent dopamine neurons from reinforcing cortico-striatal synapses that do not have a functional experiential- based value.Recurso electrónicoapplication/pdfDocumentoISSN:1932-6203http://repository.urosario.edu.co/handle/10336/8766engUniversidad del RosarioNo. 12PLOS ONEVol. 7PLOS ONE, ISSN 1932-6203, V. 7 N. 12 Dec, 2012http://www.ncbi.nlm.nih.gov.ez.urosario.edu.co/pmc/articles/PMC3527479/pdf/pone.0051610.pdfAbierto (Texto completo)EL AUTOR, manifiesta que la obra objeto de la presente autorización es original y la realizó sin violar o usurpar derechos de autor de terceros, por lo tanto la obra es de exclusiva autoría y tiene la titularidad sobre la misma.http://purl.org/coar/access_right/c_abf2instname:Universidad del Rosarioreponame:Repositorio Institucional EdocUREnfermedades616600Ganglios basalesdopaminaNeurologíaFunctional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine NeuronsarticleArtículohttp://purl.org/coar/resource_type/c_6501Ramírez-Latorre, JoséRamírez-Latorre, José A.ORIGINALFunctional Upregulation.pdfFunctional Upregulation.pdfapplication/pdf934260https://repository.urosario.edu.co/bitstreams/8aabbfcd-9659-4f7a-9ed8-3c487dca833c/downloade704113457d73ec61b9a53a62157275fMD51LICENSElicense.txtlicense.txttext/plain2156https://repository.urosario.edu.co/bitstreams/8a143232-1e2f-4d02-a39f-c79f4b64b027/downloadb4f8fe66e94b897ab4c355bac005ad16MD52TEXTFunctional Upregulation.pdf.txtFunctional Upregulation.pdf.txtExtracted texttext/plain96942https://repository.urosario.edu.co/bitstreams/871cc567-ba1e-4981-a62c-9b19bac02610/download8acfbfb923cbffe761f0f29e8da40d05MD57THUMBNAILFunctional Upregulation.pdf.jpgFunctional Upregulation.pdf.jpgGenerated Thumbnailimage/jpeg4721https://repository.urosario.edu.co/bitstreams/0e5b805e-a07b-4ac3-9f97-3a2de64f1535/download0637b360f9a3a510d4f9271e8ec73f33MD5810336/8766oai:repository.urosario.edu.co:10336/87662019-09-19 07:38:03.190837https://repository.urosario.edu.coRepositorio institucional EdocURedocur@urosario.edu.coQWN0dWFuZG8gZW4gbm9tYnJlIHByb3BpbywgZW4gY2FsaWRhZCBkZSBhdXRvciBkZWwgdHJhYmFqbyBkZSB0ZXNpcywgbW9ub2dyYWY/YSBvIHRyYWJham8gZGUgZ3JhZG8uCgpIYWdvKEhhY2Vtb3MpIGVudHJlZ2EgZGVsIGVqZW1wbGFyIHJlc3BlY3Rpdm8geSBkZSBzdXMgYW5leG9zIGVuIGZvcm1hdG8gZGlnaXRhbCBvIGVsZWN0cj9uaWNvIHkgYXV0b3Jpem8gCmEgTEEgVU5JVkVSU0lEQUQgREVMIFJPU0FSSU8sIHBhcmEgcXVlIGVuIGxvcyB0P3JtaW5vcyBlc3RhYmxlY2lkb3MgZW4gbGEgTGV5IDIzIGRlIDE5ODIsICBMZXkgNDQgZGUgMTk5MywKRGVjaXNpP24gYW5kaW5hIDM1MSBkZSAxOTkzLCBEZWNyZXRvIDQ2MCBkZSAxOTk1IHkgZGVtP3Mgbm9ybWFzIGdlbmVyYWxlcyBzb2JyZSBsYSBtYXRlcmlhLCB1dGlsaWNlIHkgdXNlCnBvciBjdWFscXVpZXIgIG1lZGlvICBjb25vY2lkbyBvIHBvciBjb25vY2VyLCBsb3MgZGVyZWNob3MgcGF0cmltb25pYWxlcyBkZSByZXByb2R1Y2NpP24sIGNvbXVuaWNhY2k/biBwPy0KYmxpY2EsdHJhbnNmb3JtYWNpP24geSBkaXN0cmlidWNpP24gcXVlIG1lIGNvcnJlc3BvbmRlbiBjb21vIGNyZWFkb3IoY3JlYWRvcmVzKSBkZSBsYSBvYnJhIG9iamV0byBkZWwgcHJlLQpzZW50ZSBkb2N1bWVudG8uIAoKUEFSQUdSQUZPOiBMYSBwcmVzZW50ZSBhdXRvcml6YWNpP24gc2UgaGFjZSBleHRlbnNpdmEgbm8gcz9sbyBhIGxhcyBmYWN1bHRhZGVzIHkgZGVyZWNob3MgZGUgdXNvIHNvYnJlIGxhCm9icmEgZW4gZm9ybWF0byBvIHNvcG9ydGUgbWF0ZXJpYWwsIHNpbm8gdGFtYmk/biBwYXJhIGZvcm1hdG8gdmlydHVhbCwgZWxlY3RyP25pY28sIGRpZ2l0YWwsID9wdGljbywgdXNvcwplbiByZWQsIGludGVybmV0LCBleHRyYW5ldCwgaW50cmFuZXQsIGV0Yy4sIHkgZW4gZ2VuZXJhbCBlbiBjdWFscXVpZXIgZm9ybWF0byBjb25vY2lkbyBvIHBvciBjb25vY2VyLgoKRUwoTE9TKSBFU1RVRElBTlRFKFMpIC0gQVVUT1IoRVMpLCBtYW5pZmllc3RhKG1hbmlmZXN0YW1vcykgcXVlIGxhIG9icmEgb2JqZXRvIGRlIGxhIHByZXNlbnRlIGF1dG9yaXphY2k/bgplcyBvcmlnaW5hbCB5IGxhIHJlYWxpemFtb3Mgc2luIHZpb2xhciBvIHVzdXJwYXIgZGVyZWNob3MgZGUgYXV0b3IgZGUgdGVyY2Vyb3MsIHBvciBsbyB0YW50byBsYSBvYnJhIGVzIGRlCmV4Y2x1c2l2YSBhdXRvcj9hIHkgdGllbmUgbGEgdGl0dWxhcmlkYWQgc29icmUgbGEgbWlzbWEuIAoKUEFSQUdSQUZPOiAgRW4gY2FzbyBkZSBwcmVzZW50YXJzZSBjdWFscXVpZXIgcmVjbGFtYWNpP24gbyBhY2NpP24gcG9yIHBhcnRlIGRlIHVuIHRlcmNlcm8gZW4gY3VhbnRvIGEgbG9zIApkZXJlY2hvcyBkZSBhdXRvciBzb2JyZSBsYSBvYnJhIGVuIGN1ZXN0aT9uLCBFTCBFU1RVRElBTlRFIC0gQVVUT1IsIGFzdW1pcmVtb3MgdG9kYSBsYSByZXNwb25zYWJpbGlkYWQsIHkKc2FsZHI/IGVuICBkZWZlbnNhICBkZSBsb3MgZGVyZWNob3MgYXF1PyBhdXRvcml6YWRvczsgcGFyYSB0b2RvcyBsb3MgZWZlY3RvcyBsYSB1bml2ZXJzaWRhZCBhY3Q/YSBjb21vIHVuIAp0ZXJjZXJvIGRlIGJ1ZW5hIGZlLiAgCgoKUE9MSVRJQ0EgREUgVFJBVEFNSUVOVE8gREUgREFUT1MgUEVSU09OQUxFUy4gRGVjbGFybyBxdWUgYXV0b3Jpem8gcHJldmlhIHkgZGUgZm9ybWEgaW5mb3JtYWRhIGVsIHRyYXRhbWllbnRvCmRlIG1pcyBkYXRvcyBwZXJzb25hbGVzIHBvciAgcGFydGUgIGRlICBMQSBVTklWRVJTSURBRCBERUwgUk9TQVJJTyAgcGFyYSBmaW5lcyBhY2FkP21pY29zIHkgZW4gYXBsaWNhY2k/biBkZQpjb252ZW5pb3MgY29uIHRlcmNlcm9zIG8gc2VydmljaW9zIGNvbmV4b3MgY29uIGFjdGl2aWRhZGVzIHByb3BpYXMgZGUgbGEgYWNhZGVtaWEsIGNvbiBlc3RyaWN0byBjdW1wbGltaWVudG8KZGUgbG9zIHByaW5jaXBpb3MgZGUgbGV5LiBQYXJhIGVsIGNvcnJlY3RvIGVqZXJjaWNpbyBkZSBtaSBkZXJlY2hvIGRlIGhhYmVhcyBkYXRhLCBjdWVudG8gIGNvbiAgbGEgY3VlbnRhIGRlCmNvcnJlbyBoYWJlYXNkYXRhQHVyb3NhcmlvLmVkdS5jbywgZG9uZGUgcHJldmlhIGlkZW50aWZpY2FjaT9uIHBvZHI/ICBzb2xpY2l0YXIgIGxhICBjb25zdWx0YSwgIGNvcnJlY2NpP24geQpzdXByZXNpP24gZGUgbWlzIGRhdG9zLgo=