Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar Organization

Summary: Neuronal activity is believed to be important for brain development; however, it remains unclear as to how spatiotemporal distributions of synaptic excitation contribute to neural network formation. Bifurcated axons of cerebellar granule cells, parallel fibers (PFs), are made in an orderly...

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Main Authors: Heeyoun Park, Taegon Kim, Jinhyun Kim, Yukio Yamamoto, Keiko Tanaka-Yamamoto
Format: Article
Language:English
Published: Elsevier 2019-09-01
Series:Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124719310435
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author Heeyoun Park
Taegon Kim
Jinhyun Kim
Yukio Yamamoto
Keiko Tanaka-Yamamoto
author_facet Heeyoun Park
Taegon Kim
Jinhyun Kim
Yukio Yamamoto
Keiko Tanaka-Yamamoto
author_sort Heeyoun Park
collection DOAJ
description Summary: Neuronal activity is believed to be important for brain development; however, it remains unclear as to how spatiotemporal distributions of synaptic excitation contribute to neural network formation. Bifurcated axons of cerebellar granule cells, parallel fibers (PFs), are made in an orderly inside-out manner during postnatal development. In this study, we induced a blockade of neurotransmitter release from specific bundles of developing PFs and tested the effects of biased PF inputs on cerebellar development. The blockade of different layers of PFs at different developmental times results in varying degrees of abnormal cerebellar development. Furthermore, cerebellar network abnormalities are not restored when PF inputs are restored in adulthood and, hence, result in motor dysfunction. We thus conclude that spatiotemporally unbiased synaptic transmission from sequentially developed PFs is crucial for cerebellar network formation and motor function, supporting the idea that unbiased excitatory synaptic transmission is crucial for network formation. : Park et al. demonstrate that interrupting synaptic transmission from a part of parallel fibers (PFs) causes abnormal cerebellar development, including Purkinje cell degeneration, reduced climbing fiber innervation, or altered interneuron positioning, which leads to motor dysfunctions. This suggests critical periods and locations of PF inputs required for cerebellar network organization. Keywords: cerebellum, granule cell, parallel fiber, Purkinje cell, motor function, postnatal development, tetanus toxin, projection-dependent labeling, climbing fiber, molecular layer interneuron
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spelling doaj.art-5e883fb3a02e4ecbac20dbd0f1f78ecc2022-12-21T20:01:10ZengElsevierCell Reports2211-12472019-09-01281129392954.e5Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar OrganizationHeeyoun Park0Taegon Kim1Jinhyun Kim2Yukio Yamamoto3Keiko Tanaka-Yamamoto4Center for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of KoreaCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of KoreaCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of KoreaCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Corresponding authorCenter for Functional Connectomics, Korea Institute of Science and Technology (KIST), Seoul 02792, Republic of Korea; Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology (UST), Seoul 02792, Republic of Korea; Corresponding authorSummary: Neuronal activity is believed to be important for brain development; however, it remains unclear as to how spatiotemporal distributions of synaptic excitation contribute to neural network formation. Bifurcated axons of cerebellar granule cells, parallel fibers (PFs), are made in an orderly inside-out manner during postnatal development. In this study, we induced a blockade of neurotransmitter release from specific bundles of developing PFs and tested the effects of biased PF inputs on cerebellar development. The blockade of different layers of PFs at different developmental times results in varying degrees of abnormal cerebellar development. Furthermore, cerebellar network abnormalities are not restored when PF inputs are restored in adulthood and, hence, result in motor dysfunction. We thus conclude that spatiotemporally unbiased synaptic transmission from sequentially developed PFs is crucial for cerebellar network formation and motor function, supporting the idea that unbiased excitatory synaptic transmission is crucial for network formation. : Park et al. demonstrate that interrupting synaptic transmission from a part of parallel fibers (PFs) causes abnormal cerebellar development, including Purkinje cell degeneration, reduced climbing fiber innervation, or altered interneuron positioning, which leads to motor dysfunctions. This suggests critical periods and locations of PF inputs required for cerebellar network organization. Keywords: cerebellum, granule cell, parallel fiber, Purkinje cell, motor function, postnatal development, tetanus toxin, projection-dependent labeling, climbing fiber, molecular layer interneuronhttp://www.sciencedirect.com/science/article/pii/S2211124719310435
spellingShingle Heeyoun Park
Taegon Kim
Jinhyun Kim
Yukio Yamamoto
Keiko Tanaka-Yamamoto
Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar Organization
Cell Reports
title Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar Organization
title_full Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar Organization
title_fullStr Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar Organization
title_full_unstemmed Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar Organization
title_short Inputs from Sequentially Developed Parallel Fibers Are Required for Cerebellar Organization
title_sort inputs from sequentially developed parallel fibers are required for cerebellar organization
url http://www.sciencedirect.com/science/article/pii/S2211124719310435
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AT taegonkim inputsfromsequentiallydevelopedparallelfibersarerequiredforcerebellarorganization
AT jinhyunkim inputsfromsequentiallydevelopedparallelfibersarerequiredforcerebellarorganization
AT yukioyamamoto inputsfromsequentiallydevelopedparallelfibersarerequiredforcerebellarorganization
AT keikotanakayamamoto inputsfromsequentiallydevelopedparallelfibersarerequiredforcerebellarorganization