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....

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Autor Principal: Ramírez-Latorre, José
Formato: Artículo (Article)
Lenguaje:Inglés (English)
Publicado: Universidad del Rosario 2012
Materias:
Acceso en línea:http://repository.urosario.edu.co/handle/10336/8766
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spelling ir-10336-87662019-09-19T12:38:03Z Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons Ramírez-Latorre, José Enfermedades Ganglios basales dopamina Neurología 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. 2012-12 2014-08-11T15:37:52Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion ISSN:1932-6203 http://repository.urosario.edu.co/handle/10336/8766 eng info:eu-repo/semantics/openAccess application/pdf Universidad del Rosario instname:Universidad del Rosario reponame:Repositorio Institucional EdocUR
institution EdocUR - Universidad del Rosario
collection DSpace
language Inglés (English)
topic Enfermedades
Ganglios basales
dopamina
Neurología
spellingShingle Enfermedades
Ganglios basales
dopamina
Neurología
Ramírez-Latorre, José
Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
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.
format Artículo (Article)
author Ramírez-Latorre, José
author_facet Ramírez-Latorre, José
author_sort Ramírez-Latorre, José
title Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons
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
publisher Universidad del Rosario
publishDate 2012
url http://repository.urosario.edu.co/handle/10336/8766
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score 11,383834