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Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing
Cerebellar climbing-fiber-mediated complex spikes originate from neurons in the inferior olive (IO), are critical for motor coordination, and are central to theories of cerebellar learning. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels expressed by IO neurons have been considere...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cell Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847187/ https://www.ncbi.nlm.nih.gov/pubmed/29444426 http://dx.doi.org/10.1016/j.celrep.2018.01.069 |
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author | Garden, Derek L.F. Oostland, Marlies Jelitai, Marta Rinaldi, Arianna Duguid, Ian Nolan, Matthew F. |
author_facet | Garden, Derek L.F. Oostland, Marlies Jelitai, Marta Rinaldi, Arianna Duguid, Ian Nolan, Matthew F. |
author_sort | Garden, Derek L.F. |
collection | PubMed |
description | Cerebellar climbing-fiber-mediated complex spikes originate from neurons in the inferior olive (IO), are critical for motor coordination, and are central to theories of cerebellar learning. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels expressed by IO neurons have been considered as pacemaker currents important for oscillatory and resonant dynamics. Here, we demonstrate that in vitro, network actions of HCN1 channels enable bidirectional glutamatergic synaptic responses, while local actions of HCN1 channels determine the timing and waveform of synaptically driven action potentials. These roles are distinct from, and may complement, proposed pacemaker functions of HCN channels. We find that in behaving animals HCN1 channels reduce variability in the timing of cerebellar complex spikes, which serve as a readout of IO spiking. Our results suggest that spatially distributed actions of HCN1 channels enable the IO to implement network-wide rules for synaptic integration that modulate the timing of cerebellar climbing fiber signals. |
format | Online Article Text |
id | pubmed-5847187 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Cell Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-58471872018-03-13 Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing Garden, Derek L.F. Oostland, Marlies Jelitai, Marta Rinaldi, Arianna Duguid, Ian Nolan, Matthew F. Cell Rep Article Cerebellar climbing-fiber-mediated complex spikes originate from neurons in the inferior olive (IO), are critical for motor coordination, and are central to theories of cerebellar learning. Hyperpolarization-activated cyclic-nucleotide-gated (HCN) channels expressed by IO neurons have been considered as pacemaker currents important for oscillatory and resonant dynamics. Here, we demonstrate that in vitro, network actions of HCN1 channels enable bidirectional glutamatergic synaptic responses, while local actions of HCN1 channels determine the timing and waveform of synaptically driven action potentials. These roles are distinct from, and may complement, proposed pacemaker functions of HCN channels. We find that in behaving animals HCN1 channels reduce variability in the timing of cerebellar complex spikes, which serve as a readout of IO spiking. Our results suggest that spatially distributed actions of HCN1 channels enable the IO to implement network-wide rules for synaptic integration that modulate the timing of cerebellar climbing fiber signals. Cell Press 2018-02-13 /pmc/articles/PMC5847187/ /pubmed/29444426 http://dx.doi.org/10.1016/j.celrep.2018.01.069 Text en © 2018 The Authors 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 Garden, Derek L.F. Oostland, Marlies Jelitai, Marta Rinaldi, Arianna Duguid, Ian Nolan, Matthew F. Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing |
title | Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing |
title_full | Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing |
title_fullStr | Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing |
title_full_unstemmed | Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing |
title_short | Inferior Olive HCN1 Channels Coordinate Synaptic Integration and Complex Spike Timing |
title_sort | inferior olive hcn1 channels coordinate synaptic integration and complex spike timing |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5847187/ https://www.ncbi.nlm.nih.gov/pubmed/29444426 http://dx.doi.org/10.1016/j.celrep.2018.01.069 |
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