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Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation

Cholinergic interneurons (ChIs) of the striatum pause their firing in response to salient stimuli and conditioned stimuli after learning. Several different mechanisms for pause generation have been proposed, but a unifying basis has not previously emerged. Here, using in vivo and ex vivo recordings...

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Detalles Bibliográficos
Autores principales: Zhang, Yan-Feng, Reynolds, John N.J., Cragg, Stephanie J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993868/
https://www.ncbi.nlm.nih.gov/pubmed/29754751
http://dx.doi.org/10.1016/j.neuron.2018.04.027
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author Zhang, Yan-Feng
Reynolds, John N.J.
Cragg, Stephanie J.
author_facet Zhang, Yan-Feng
Reynolds, John N.J.
Cragg, Stephanie J.
author_sort Zhang, Yan-Feng
collection PubMed
description Cholinergic interneurons (ChIs) of the striatum pause their firing in response to salient stimuli and conditioned stimuli after learning. Several different mechanisms for pause generation have been proposed, but a unifying basis has not previously emerged. Here, using in vivo and ex vivo recordings in rat and mouse brain and a computational model, we show that ChI pauses are driven by withdrawal of excitatory inputs to striatum and result from a delayed rectifier potassium current (I(Kr)) in concert with local neuromodulation. The I(Kr) is sensitive to K(v)7.2/7.3 blocker XE-991 and enables ChIs to report changes in input, to pause on excitatory input recession, and to scale pauses with input strength, in keeping with pause acquisition during learning. We also show that although dopamine can hyperpolarize ChIs directly, its augmentation of pauses is best explained by strengthening excitatory inputs. These findings provide a basis to understand pause generation in striatal ChIs. VIDEO ABSTRACT:
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spelling pubmed-59938682018-06-11 Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation Zhang, Yan-Feng Reynolds, John N.J. Cragg, Stephanie J. Neuron Article Cholinergic interneurons (ChIs) of the striatum pause their firing in response to salient stimuli and conditioned stimuli after learning. Several different mechanisms for pause generation have been proposed, but a unifying basis has not previously emerged. Here, using in vivo and ex vivo recordings in rat and mouse brain and a computational model, we show that ChI pauses are driven by withdrawal of excitatory inputs to striatum and result from a delayed rectifier potassium current (I(Kr)) in concert with local neuromodulation. The I(Kr) is sensitive to K(v)7.2/7.3 blocker XE-991 and enables ChIs to report changes in input, to pause on excitatory input recession, and to scale pauses with input strength, in keeping with pause acquisition during learning. We also show that although dopamine can hyperpolarize ChIs directly, its augmentation of pauses is best explained by strengthening excitatory inputs. These findings provide a basis to understand pause generation in striatal ChIs. VIDEO ABSTRACT: Cell Press 2018-06-06 /pmc/articles/PMC5993868/ /pubmed/29754751 http://dx.doi.org/10.1016/j.neuron.2018.04.027 Text en © 2018 The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Yan-Feng
Reynolds, John N.J.
Cragg, Stephanie J.
Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation
title Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation
title_full Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation
title_fullStr Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation
title_full_unstemmed Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation
title_short Pauses in Cholinergic Interneuron Activity Are Driven by Excitatory Input and Delayed Rectification, with Dopamine Modulation
title_sort pauses in cholinergic interneuron activity are driven by excitatory input and delayed rectification, with dopamine modulation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5993868/
https://www.ncbi.nlm.nih.gov/pubmed/29754751
http://dx.doi.org/10.1016/j.neuron.2018.04.027
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