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/10336/8838
id ir-10336-8838
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spelling ir-10336-88382019-09-19T12:37:54Z Functional Upregulation of Ca2+ -Activated K+ Channels in the Development of Substantia Nigra Dopamine Neurons Ramírez Latorre, José Fisiología humana PARS COMPACTA NEURONS BASAL GANGLIA POTASSIUM CHANNELS CALCIUM-CHANNELS HIGH-FREQUENCY BK CHANNELS BK CHANNELS IN-VITRO IN-VITRO PARASYMPATHETIC NEURONS POSTNATAL-DEVELOPMENT NEONATAL-RATS Dopamina Neuronas Sinapsis Neurología Bioquímica 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 Ca2+, TEA, BK, and SK blockers. Rapidly after birth, the outward current increases to 15nS-V and becomes sensitive to Ca2+, 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 Ca2+ channels in clusters. In the first cluster, T-type Ca2+ and BK channels are coupled within distances of similar to 20 nm (200 parallel to). The second cluster consists of L-type Ca2+ 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. 2012-12-20 2014-08-13T19:00:17Z info:eu-repo/semantics/article info:eu-repo/semantics/acceptedVersion ISSN:1932-6203 http://repository.urosario.edu.co/handle/10336/8838 eng info:eu-repo/semantics/openAccess application/pdf Universidad del Rosario reponame:Repositorio Institucional EdocUR instname:Universidad del Rosario
institution EdocUR - Universidad del Rosario
collection DSpace
language Inglés (English)
topic Fisiología humana
PARS COMPACTA NEURONS
BASAL GANGLIA
POTASSIUM CHANNELS
CALCIUM-CHANNELS
HIGH-FREQUENCY
BK CHANNELS
BK CHANNELS
IN-VITRO
IN-VITRO
PARASYMPATHETIC NEURONS
POSTNATAL-DEVELOPMENT
NEONATAL-RATS
Dopamina
Neuronas
Sinapsis
Neurología
Bioquímica
spellingShingle Fisiología humana
PARS COMPACTA NEURONS
BASAL GANGLIA
POTASSIUM CHANNELS
CALCIUM-CHANNELS
HIGH-FREQUENCY
BK CHANNELS
BK CHANNELS
IN-VITRO
IN-VITRO
PARASYMPATHETIC NEURONS
POSTNATAL-DEVELOPMENT
NEONATAL-RATS
Dopamina
Neuronas
Sinapsis
Neurología
Bioquímica
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 Ca2+, TEA, BK, and SK blockers. Rapidly after birth, the outward current increases to 15nS-V and becomes sensitive to Ca2+, 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 Ca2+ channels in clusters. In the first cluster, T-type Ca2+ and BK channels are coupled within distances of similar to 20 nm (200 parallel to). The second cluster consists of L-type Ca2+ 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/10336/8838
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score 10,662579