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A system of feed-forward cerebellar circuits that extend and diversify sensory signaling

Sensory signals are processed by the cerebellum to coordinate movements. Numerous cerebellar functions are thought to require the maintenance of a sensory representation that extends beyond the input signal. Granule cells receive sensory input, but they do not prolong the signal and are thus unlikel...

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Autores principales: Hariani, Harsh N., Algstam, A. Brynn, Candler, Christian T., Witteveen, Isabelle F., Sidhu, Jasmeen K., Balmer, Timothy S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120650/
https://www.ncbi.nlm.nih.gov/pubmed/37090638
http://dx.doi.org/10.1101/2023.04.11.536335
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author Hariani, Harsh N.
Algstam, A. Brynn
Candler, Christian T.
Witteveen, Isabelle F.
Sidhu, Jasmeen K.
Balmer, Timothy S.
author_facet Hariani, Harsh N.
Algstam, A. Brynn
Candler, Christian T.
Witteveen, Isabelle F.
Sidhu, Jasmeen K.
Balmer, Timothy S.
author_sort Hariani, Harsh N.
collection PubMed
description Sensory signals are processed by the cerebellum to coordinate movements. Numerous cerebellar functions are thought to require the maintenance of a sensory representation that extends beyond the input signal. Granule cells receive sensory input, but they do not prolong the signal and are thus unlikely to maintain a sensory representation for much longer than the inputs themselves. Unipolar brush cells (UBCs) are excitatory interneurons that project to granule cells and transform sensory input into prolonged increases or decreases in firing, depending on their ON or OFF UBC subtype. Further extension and diversification of the input signal could be produced by UBCs that project to one another, but whether this circuitry exists is unclear. Here we test whether UBCs innervate one another and explore how these small networks of UBCs could transform spiking patterns. We characterized two transgenic mouse lines electrophysiologically and immunohistochemically to confirm that they label ON and OFF UBC subtypes and crossed them together, revealing that ON and OFF UBCs innervate one another. A Brainbow reporter was used to label UBCs of the same ON or OFF subtype with different fluorescent proteins, which showed that UBCs innervate their own subtypes as well. Computational models predict that these feed-forward networks of UBCs extend the length of bursts or pauses and introduce delays—transformations that may be necessary for cerebellar functions from modulation of eye movements to adaptive learning across time scales.
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spelling pubmed-101206502023-04-22 A system of feed-forward cerebellar circuits that extend and diversify sensory signaling Hariani, Harsh N. Algstam, A. Brynn Candler, Christian T. Witteveen, Isabelle F. Sidhu, Jasmeen K. Balmer, Timothy S. bioRxiv Article Sensory signals are processed by the cerebellum to coordinate movements. Numerous cerebellar functions are thought to require the maintenance of a sensory representation that extends beyond the input signal. Granule cells receive sensory input, but they do not prolong the signal and are thus unlikely to maintain a sensory representation for much longer than the inputs themselves. Unipolar brush cells (UBCs) are excitatory interneurons that project to granule cells and transform sensory input into prolonged increases or decreases in firing, depending on their ON or OFF UBC subtype. Further extension and diversification of the input signal could be produced by UBCs that project to one another, but whether this circuitry exists is unclear. Here we test whether UBCs innervate one another and explore how these small networks of UBCs could transform spiking patterns. We characterized two transgenic mouse lines electrophysiologically and immunohistochemically to confirm that they label ON and OFF UBC subtypes and crossed them together, revealing that ON and OFF UBCs innervate one another. A Brainbow reporter was used to label UBCs of the same ON or OFF subtype with different fluorescent proteins, which showed that UBCs innervate their own subtypes as well. Computational models predict that these feed-forward networks of UBCs extend the length of bursts or pauses and introduce delays—transformations that may be necessary for cerebellar functions from modulation of eye movements to adaptive learning across time scales. Cold Spring Harbor Laboratory 2023-09-14 /pmc/articles/PMC10120650/ /pubmed/37090638 http://dx.doi.org/10.1101/2023.04.11.536335 Text en https://creativecommons.org/licenses/by/4.0/This work is licensed under a Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/) , which allows reusers to distribute, remix, adapt, and build upon the material in any medium or format, so long as attribution is given to the creator. The license allows for commercial use.
spellingShingle Article
Hariani, Harsh N.
Algstam, A. Brynn
Candler, Christian T.
Witteveen, Isabelle F.
Sidhu, Jasmeen K.
Balmer, Timothy S.
A system of feed-forward cerebellar circuits that extend and diversify sensory signaling
title A system of feed-forward cerebellar circuits that extend and diversify sensory signaling
title_full A system of feed-forward cerebellar circuits that extend and diversify sensory signaling
title_fullStr A system of feed-forward cerebellar circuits that extend and diversify sensory signaling
title_full_unstemmed A system of feed-forward cerebellar circuits that extend and diversify sensory signaling
title_short A system of feed-forward cerebellar circuits that extend and diversify sensory signaling
title_sort system of feed-forward cerebellar circuits that extend and diversify sensory signaling
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10120650/
https://www.ncbi.nlm.nih.gov/pubmed/37090638
http://dx.doi.org/10.1101/2023.04.11.536335
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