Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum

Abstract The long-standing hypothesis that synapses between mossy fibers (MFs) and cerebellar granule cells (GCs) are organized according to the origins of MFs and locations of GC axons, parallel fibers (PFs), is supported by recent findings. However, the mechanisms of such organized synaptic connec...

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Main Authors: Taegon Kim, Heeyoun Park, Keiko Tanaka-Yamamoto, Yukio Yamamoto
Format: Article
Language:English
Published: Nature Portfolio 2023-04-01
Series:Communications Biology
Online Access:https://doi.org/10.1038/s42003-023-04825-y
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author Taegon Kim
Heeyoun Park
Keiko Tanaka-Yamamoto
Yukio Yamamoto
author_facet Taegon Kim
Heeyoun Park
Keiko Tanaka-Yamamoto
Yukio Yamamoto
author_sort Taegon Kim
collection DOAJ
description Abstract The long-standing hypothesis that synapses between mossy fibers (MFs) and cerebellar granule cells (GCs) are organized according to the origins of MFs and locations of GC axons, parallel fibers (PFs), is supported by recent findings. However, the mechanisms of such organized synaptic connections remain unknown. Here, using our technique that enabled PF location-dependent labeling of GCs in mice, we confirmed that synaptic connections of GCs with specific MFs originating from the pontine nucleus (PN-MFs) and dorsal column nuclei (DCoN-MFs) were gently but differentially organized according to their PF locations. We then found that overall MF-GC synaptic connectivity was biased in a way that dendrites of GCs having nearby PFs tended to connect with the same MF terminals, implying that the MF origin- and PF location-dependent organization is associated with the overall biased MF-GC synaptic connectivity. Furthermore, the development of PN-MFs preceded that of DCoN-MFs, which matches the developmental sequence of GCs that preferentially connect with each type of these MFs. Thus, our results revealed that overall MF-GC synaptic connectivity is biased in terms of PF locations, and suggested that such connectivity is likely the result of synaptic formation between developmental timing-matched partners.
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spelling doaj.art-6ec042ab518e4a0e88decd4421e4e8102023-04-30T11:24:34ZengNature PortfolioCommunications Biology2399-36422023-04-016111810.1038/s42003-023-04825-yDevelopmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellumTaegon Kim0Heeyoun Park1Keiko Tanaka-Yamamoto2Yukio Yamamoto3Brain Science Institute, Korea Institute of Science and Technology (KIST)Brain Science Institute, Korea Institute of Science and Technology (KIST)Brain Science Institute, Korea Institute of Science and Technology (KIST)Brain Science Institute, Korea Institute of Science and Technology (KIST)Abstract The long-standing hypothesis that synapses between mossy fibers (MFs) and cerebellar granule cells (GCs) are organized according to the origins of MFs and locations of GC axons, parallel fibers (PFs), is supported by recent findings. However, the mechanisms of such organized synaptic connections remain unknown. Here, using our technique that enabled PF location-dependent labeling of GCs in mice, we confirmed that synaptic connections of GCs with specific MFs originating from the pontine nucleus (PN-MFs) and dorsal column nuclei (DCoN-MFs) were gently but differentially organized according to their PF locations. We then found that overall MF-GC synaptic connectivity was biased in a way that dendrites of GCs having nearby PFs tended to connect with the same MF terminals, implying that the MF origin- and PF location-dependent organization is associated with the overall biased MF-GC synaptic connectivity. Furthermore, the development of PN-MFs preceded that of DCoN-MFs, which matches the developmental sequence of GCs that preferentially connect with each type of these MFs. Thus, our results revealed that overall MF-GC synaptic connectivity is biased in terms of PF locations, and suggested that such connectivity is likely the result of synaptic formation between developmental timing-matched partners.https://doi.org/10.1038/s42003-023-04825-y
spellingShingle Taegon Kim
Heeyoun Park
Keiko Tanaka-Yamamoto
Yukio Yamamoto
Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum
Communications Biology
title Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum
title_full Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum
title_fullStr Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum
title_full_unstemmed Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum
title_short Developmental timing-dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum
title_sort developmental timing dependent organization of synaptic connections between mossy fibers and granule cells in the cerebellum
url https://doi.org/10.1038/s42003-023-04825-y
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