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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...

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Autores principales: Garden, Derek L.F., Oostland, Marlies, Jelitai, Marta, Rinaldi, Arianna, Duguid, Ian, Nolan, Matthew F.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2018
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.
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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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