Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus

Cerebellar malformations cause changes to the sleep-wake cycle, resulting in sleep disturbance. However, it is unclear how the cerebellum contributes to the sleep-wake cycle. To examine the neural connections between the cerebellum and the nuclei involved in the sleep-wake cycle, we investigated the...

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Main Authors: Mitsuhiro Hashimoto, Akihiro Yamanaka, Shigeki Kato, Manabu Tanifuji, Kazuto Kobayashi, Hiroyuki Yaginuma
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-02-01
Series:Frontiers in Neural Circuits
Subjects:
Online Access:http://journal.frontiersin.org/article/10.3389/fncir.2018.00006/full
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author Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Akihiro Yamanaka
Shigeki Kato
Manabu Tanifuji
Manabu Tanifuji
Manabu Tanifuji
Kazuto Kobayashi
Hiroyuki Yaginuma
author_facet Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Akihiro Yamanaka
Shigeki Kato
Manabu Tanifuji
Manabu Tanifuji
Manabu Tanifuji
Kazuto Kobayashi
Hiroyuki Yaginuma
author_sort Mitsuhiro Hashimoto
collection DOAJ
description Cerebellar malformations cause changes to the sleep-wake cycle, resulting in sleep disturbance. However, it is unclear how the cerebellum contributes to the sleep-wake cycle. To examine the neural connections between the cerebellum and the nuclei involved in the sleep-wake cycle, we investigated the axonal projections of Purkinje cells in the mouse posterior vermis by using an adeno-associated virus (AAV) vector (serotype rh10) as an anterograde tracer. When an AAV vector expressing humanized renilla green fluorescent protein was injected into the cerebellar lobule IX, hrGFP and synaptophysin double-positive axonal terminals were observed in the region of medial parabrachial nucleus (MPB). The MPB is involved in the phase transition from rapid eye movement (REM) sleep to Non-REM sleep and vice versa, and the cardiovascular and respiratory responses. The hrGFP-positive axons from lobule IX went through the ventral spinocerebellar tract and finally reached the MPB. By contrast, when the AAV vector was injected into cerebellar lobule VI, no hrGFP-positive axons were observed in the MPB. To examine neurons projecting to the MPB, we unilaterally injected Fast Blue and AAV vector (retrograde serotype, rAAV2-retro) as retrograde tracers into the MPB. The cerebellar Purkinje cells in lobules VIII–X on the ipsilateral side of the Fast Blue-injected MPB were retrogradely labeled by Fast Blue and AAV vector (retrograde serotype), but no retrograde-labeled Purkinje cells were observed in lobules VI–VII and the cerebellar hemispheres. These results indicated that Purkinje cells in lobules VIII–X directly project their axons to the ipsilateral MPB but not lobules VI–VII. The direct connection between lobules VIII–X and the MPB suggests that the cerebellum participates in the neural network controlling the sleep-wake cycle, and cardiovascular and respiratory responses, by modulating the physiological function of the MPB.
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spelling doaj.art-909385b37cb24a4cbb0a09e4ebdfd7b72022-12-22T01:37:52ZengFrontiers Media S.A.Frontiers in Neural Circuits1662-51102018-02-011210.3389/fncir.2018.00006245722Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial NucleusMitsuhiro Hashimoto0Mitsuhiro Hashimoto1Mitsuhiro Hashimoto2Mitsuhiro Hashimoto3Akihiro Yamanaka4Shigeki Kato5Manabu Tanifuji6Manabu Tanifuji7Manabu Tanifuji8Kazuto Kobayashi9Hiroyuki Yaginuma10Department of Neuroanatomy and Embryology, Fukushima Medical University Graduate School of Medicine, Fukushima, JapanBrain Interdisciplinary Research Division, Research Institute for Science and Technology, Tokyo University of Science, Noda-shi, JapanDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya-shi, JapanLaboratory for Integrative Neural Systems, RIKEN Brain Science Institute, Saitama, JapanDepartment of Neuroscience II, Research Institute of Environmental Medicine, Nagoya University, Nagoya-shi, JapanDepartment of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University Graduate School of Medicine, Fukushima, JapanLaboratory for Integrative Neural Systems, RIKEN Brain Science Institute, Saitama, JapanDepartment of Life Science and Medical Bio-Science, Faculty of Science and Engineering, Waseda University, Tokyo, JapanDepartment of Complexity Science and Engineering, Graduate School of Frontier Sciences, University of Tokyo, Kashiwa, JapanDepartment of Molecular Genetics, Institute of Biomedical Sciences, Fukushima Medical University Graduate School of Medicine, Fukushima, JapanDepartment of Neuroanatomy and Embryology, Fukushima Medical University Graduate School of Medicine, Fukushima, JapanCerebellar malformations cause changes to the sleep-wake cycle, resulting in sleep disturbance. However, it is unclear how the cerebellum contributes to the sleep-wake cycle. To examine the neural connections between the cerebellum and the nuclei involved in the sleep-wake cycle, we investigated the axonal projections of Purkinje cells in the mouse posterior vermis by using an adeno-associated virus (AAV) vector (serotype rh10) as an anterograde tracer. When an AAV vector expressing humanized renilla green fluorescent protein was injected into the cerebellar lobule IX, hrGFP and synaptophysin double-positive axonal terminals were observed in the region of medial parabrachial nucleus (MPB). The MPB is involved in the phase transition from rapid eye movement (REM) sleep to Non-REM sleep and vice versa, and the cardiovascular and respiratory responses. The hrGFP-positive axons from lobule IX went through the ventral spinocerebellar tract and finally reached the MPB. By contrast, when the AAV vector was injected into cerebellar lobule VI, no hrGFP-positive axons were observed in the MPB. To examine neurons projecting to the MPB, we unilaterally injected Fast Blue and AAV vector (retrograde serotype, rAAV2-retro) as retrograde tracers into the MPB. The cerebellar Purkinje cells in lobules VIII–X on the ipsilateral side of the Fast Blue-injected MPB were retrogradely labeled by Fast Blue and AAV vector (retrograde serotype), but no retrograde-labeled Purkinje cells were observed in lobules VI–VII and the cerebellar hemispheres. These results indicated that Purkinje cells in lobules VIII–X directly project their axons to the ipsilateral MPB but not lobules VI–VII. The direct connection between lobules VIII–X and the MPB suggests that the cerebellum participates in the neural network controlling the sleep-wake cycle, and cardiovascular and respiratory responses, by modulating the physiological function of the MPB.http://journal.frontiersin.org/article/10.3389/fncir.2018.00006/fullcerebellum circuitsmedial parabrachial nucleusaden-associated virusretrograde tracinganterograde tracingcerebellar vermis
spellingShingle Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Mitsuhiro Hashimoto
Akihiro Yamanaka
Shigeki Kato
Manabu Tanifuji
Manabu Tanifuji
Manabu Tanifuji
Kazuto Kobayashi
Hiroyuki Yaginuma
Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus
Frontiers in Neural Circuits
cerebellum circuits
medial parabrachial nucleus
aden-associated virus
retrograde tracing
anterograde tracing
cerebellar vermis
title Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus
title_full Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus
title_fullStr Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus
title_full_unstemmed Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus
title_short Anatomical Evidence for a Direct Projection from Purkinje Cells in the Mouse Cerebellar Vermis to Medial Parabrachial Nucleus
title_sort anatomical evidence for a direct projection from purkinje cells in the mouse cerebellar vermis to medial parabrachial nucleus
topic cerebellum circuits
medial parabrachial nucleus
aden-associated virus
retrograde tracing
anterograde tracing
cerebellar vermis
url http://journal.frontiersin.org/article/10.3389/fncir.2018.00006/full
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