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

Ramírez-Latorre, José

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

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dc.audience	Comunidad Rosarista	spa
dc.creator	Ramírez-Latorre, José
dc.creator.google	Ramírez-Latorre, José A.
dc.date.accessioned	2014-08-11T15:37:52Z
dc.date.available	2014-08-11T15:37:52Z
dc.date.created	2012-12
dc.date.issued	2012
dc.description.abstract	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.	eng
dc.format.medium	Recurso electrónico	spa
dc.format.mimetype	application/pdf
dc.format.tipo	Documento	spa
dc.identifier.issn	ISSN:1932-6203
dc.identifier.uri	http://repository.urosario.edu.co/handle/10336/8766
dc.language.iso	eng
dc.publisher	Universidad del Rosario	spa
dc.relation.citationIssue	No. 12
dc.relation.citationTitle	PLOS ONE
dc.relation.citationVolume	Vol. 7
dc.relation.ispartof	PLOS ONE, ISSN 1932-6203, V. 7 N. 12 Dec, 2012	spa
dc.relation.uri	http://www.ncbi.nlm.nih.gov.ez.urosario.edu.co/pmc/articles/PMC3527479/pdf/pone.0051610.pdf
dc.rights.accesRights	info:eu-repo/semantics/openAccess
dc.rights.acceso	Abierto (Texto completo)	spa
dc.rights.licencia	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.	spa
dc.source.instname	instname:Universidad del Rosario	spa
dc.source.reponame	reponame:Repositorio Institucional EdocUR	spa
dc.subject.ddc	Enfermedades
dc.subject.decs	Ganglios basales	spa
dc.subject.decs	dopamina	spa
dc.subject.decs	Neurología	spa
dc.title	Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons	spa
dc.type	article	eng
dc.type.hasVersion	info:eu-repo/semantics/acceptedVersion
dc.type.spa	Artículo	spa