Motor and non-motor control by neuronal subpopulations within the deep cerebellum

The cerebellum is linked to a multitude of regions in the brain and spinal cord, projecting to at least twenty-seven brain regions, to control a diverse array of motor and non-motor processes. Embedded within lies the cerebellar nuclei which receive, integrate and transmit diverse sensorimotor infor...

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Main Author: Low, Aloysius Yeow Teck
Other Authors: Albert I. Chen
Format: Theses and Dissertations
Language:English
Published: 2019
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Online Access:https://hdl.handle.net/10356/88172
http://hdl.handle.net/10220/47424
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Institution: Nanyang Technological University
Language: English
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spelling sg-ntu-dr.10356-881722020-11-01T04:51:17Z Motor and non-motor control by neuronal subpopulations within the deep cerebellum Low, Aloysius Yeow Teck Albert I. Chen Interdisciplinary Graduate School (IGS) DRNTU::Science::Biological sciences The cerebellum is linked to a multitude of regions in the brain and spinal cord, projecting to at least twenty-seven brain regions, to control a diverse array of motor and non-motor processes. Embedded within lies the cerebellar nuclei which receive, integrate and transmit diverse sensorimotor information to relevant brain regions. However, the functional relevance of identifiable neuronal subpopulations within the cerebellar nuclei remains unclear. To explore the mechanisms underlying the function of the cerebellar nuclei, we examined a subset of genetically tractable neurons in the mouse cerebellar interposed nucleus, and studied the involvement of these neurons in discrete and rhythmic limb movements, and in feeding-related tasks. Analysis of the connectivity and function of these neurons through tract tracing and optogenetic experiments revealed that a subset of glutamatergic neurons in the anterior cerebellar interposed nucleus can be labeled with the Urocortin 3::Cre mouse line, and that these neurons constitute a specific element of an internal feedback circuit within the cerebellum and cerebello-thalamo-cortical pathway associated with limb control. Additionally, through trans-synaptic and anterograde/retrograde tracing analysis, we found that neurons in the interposed nucleus also belong to the cerebello-subthalamic-hypothalamic pathway which may be involved in non-motor processes. Chemogenetic manipulation of neurons in the interposed nucleus revealed that the activity of neurons in the arcuate nucleus and feeding behavior also depend on neurons in the interposed nucleus. In summary, we show that target selectivity may be a key distinguishing property among neuronal subpopulations in the cerebellar nuclei, and illustrate the diversity and complexity of intra- and extra-cerebellar connections made by neurons in the cerebellar nuclei. In agreement with the notion that the cerebellum modulates both motor and non-motor functions, our study links different subpopulations of glutamatergic neurons in the interposed nucleus and their unique circuitry with coordination of precise and effective movements, as well as mediation of feeding-related response. Doctor of Philosophy 2019-01-08T06:01:17Z 2019-12-06T16:57:41Z 2019-01-08T06:01:17Z 2019-12-06T16:57:41Z 2018 Thesis Low, A. Y. T. (2018). Motor and non-motor control by neuronal subpopulations within the deep cerebellum. Doctoral thesis, Nanyang Technological University, Singapore. https://hdl.handle.net/10356/88172 http://hdl.handle.net/10220/47424 10.32657/10220/47424 en 191 p. application/pdf
institution Nanyang Technological University
building NTU Library
continent Asia
country Singapore
Singapore
content_provider NTU Library
collection DR-NTU
language English
topic DRNTU::Science::Biological sciences
spellingShingle DRNTU::Science::Biological sciences
Low, Aloysius Yeow Teck
Motor and non-motor control by neuronal subpopulations within the deep cerebellum
description The cerebellum is linked to a multitude of regions in the brain and spinal cord, projecting to at least twenty-seven brain regions, to control a diverse array of motor and non-motor processes. Embedded within lies the cerebellar nuclei which receive, integrate and transmit diverse sensorimotor information to relevant brain regions. However, the functional relevance of identifiable neuronal subpopulations within the cerebellar nuclei remains unclear. To explore the mechanisms underlying the function of the cerebellar nuclei, we examined a subset of genetically tractable neurons in the mouse cerebellar interposed nucleus, and studied the involvement of these neurons in discrete and rhythmic limb movements, and in feeding-related tasks. Analysis of the connectivity and function of these neurons through tract tracing and optogenetic experiments revealed that a subset of glutamatergic neurons in the anterior cerebellar interposed nucleus can be labeled with the Urocortin 3::Cre mouse line, and that these neurons constitute a specific element of an internal feedback circuit within the cerebellum and cerebello-thalamo-cortical pathway associated with limb control. Additionally, through trans-synaptic and anterograde/retrograde tracing analysis, we found that neurons in the interposed nucleus also belong to the cerebello-subthalamic-hypothalamic pathway which may be involved in non-motor processes. Chemogenetic manipulation of neurons in the interposed nucleus revealed that the activity of neurons in the arcuate nucleus and feeding behavior also depend on neurons in the interposed nucleus. In summary, we show that target selectivity may be a key distinguishing property among neuronal subpopulations in the cerebellar nuclei, and illustrate the diversity and complexity of intra- and extra-cerebellar connections made by neurons in the cerebellar nuclei. In agreement with the notion that the cerebellum modulates both motor and non-motor functions, our study links different subpopulations of glutamatergic neurons in the interposed nucleus and their unique circuitry with coordination of precise and effective movements, as well as mediation of feeding-related response.
author2 Albert I. Chen
author_facet Albert I. Chen
Low, Aloysius Yeow Teck
format Theses and Dissertations
author Low, Aloysius Yeow Teck
author_sort Low, Aloysius Yeow Teck
title Motor and non-motor control by neuronal subpopulations within the deep cerebellum
title_short Motor and non-motor control by neuronal subpopulations within the deep cerebellum
title_full Motor and non-motor control by neuronal subpopulations within the deep cerebellum
title_fullStr Motor and non-motor control by neuronal subpopulations within the deep cerebellum
title_full_unstemmed Motor and non-motor control by neuronal subpopulations within the deep cerebellum
title_sort motor and non-motor control by neuronal subpopulations within the deep cerebellum
publishDate 2019
url https://hdl.handle.net/10356/88172
http://hdl.handle.net/10220/47424
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