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Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning
Thyrotropin-releasing hormone (TRH) regulates various physiological activities through activation of receptors expressed in a broad range of cells in the central nervous system. The cerebellum expresses TRH receptors in granule cells and molecular layer interneurons. However, the function of TRH in...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299015/ https://www.ncbi.nlm.nih.gov/pubmed/30618637 http://dx.doi.org/10.3389/fncel.2018.00490 |
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author | Watanave, Masashi Matsuzaki, Yasunori Nakajima, Yasuyo Ozawa, Atsushi Yamada, Masanobu Hirai, Hirokazu |
author_facet | Watanave, Masashi Matsuzaki, Yasunori Nakajima, Yasuyo Ozawa, Atsushi Yamada, Masanobu Hirai, Hirokazu |
author_sort | Watanave, Masashi |
collection | PubMed |
description | Thyrotropin-releasing hormone (TRH) regulates various physiological activities through activation of receptors expressed in a broad range of cells in the central nervous system. The cerebellum expresses TRH receptors in granule cells and molecular layer interneurons. However, the function of TRH in the cerebellum remains to be clarified. Here, using TRH knockout (KO) mice we studied the role of TRH in the cerebellum. Immunohistochemistry showed no gross morphological differences between KO mice and wild-type (WT) littermates in the cerebellum. In the rotarod test, the initial performance of KO mice was comparable to that of WT littermates, but the learning speed of KO mice was significantly lower than that of WT littermates, suggesting impaired motor learning. The motor learning deficit in KO mice was rescued by intraperitoneal injection of TRH. Electrophysiology revealed absence of long-term depression (LTD) at parallel fiber-Purkinje cell synapses in KO mice, which was rescued by bath-application of TRH. TRH was shown to increase cyclic guanosine monophosphate (cGMP) content in the cerebellum. Since nitric oxide (NO) stimulates cGMP synthesis in the cerebellum, we examined whether NO-cGMP pathway was involved in TRH-mediated LTD rescue in KO mice. Pharmacological blockade of NO synthase and subsequent cGMP production prevented TRH-induced LTD expression in KO mice, whereas increase in cGMP signal in Purkinje cells by 8-bromoguanosine cyclic 3’,5’-monophosphate, a membrane-permeable cGMP analog, restored LTD without TRH application. These results suggest that TRH is involved in cerebellar LTD presumably by upregulating the basal cGMP level in Purkinje cells, and, consequently, in motor learning. |
format | Online Article Text |
id | pubmed-6299015 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-62990152019-01-07 Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning Watanave, Masashi Matsuzaki, Yasunori Nakajima, Yasuyo Ozawa, Atsushi Yamada, Masanobu Hirai, Hirokazu Front Cell Neurosci Neuroscience Thyrotropin-releasing hormone (TRH) regulates various physiological activities through activation of receptors expressed in a broad range of cells in the central nervous system. The cerebellum expresses TRH receptors in granule cells and molecular layer interneurons. However, the function of TRH in the cerebellum remains to be clarified. Here, using TRH knockout (KO) mice we studied the role of TRH in the cerebellum. Immunohistochemistry showed no gross morphological differences between KO mice and wild-type (WT) littermates in the cerebellum. In the rotarod test, the initial performance of KO mice was comparable to that of WT littermates, but the learning speed of KO mice was significantly lower than that of WT littermates, suggesting impaired motor learning. The motor learning deficit in KO mice was rescued by intraperitoneal injection of TRH. Electrophysiology revealed absence of long-term depression (LTD) at parallel fiber-Purkinje cell synapses in KO mice, which was rescued by bath-application of TRH. TRH was shown to increase cyclic guanosine monophosphate (cGMP) content in the cerebellum. Since nitric oxide (NO) stimulates cGMP synthesis in the cerebellum, we examined whether NO-cGMP pathway was involved in TRH-mediated LTD rescue in KO mice. Pharmacological blockade of NO synthase and subsequent cGMP production prevented TRH-induced LTD expression in KO mice, whereas increase in cGMP signal in Purkinje cells by 8-bromoguanosine cyclic 3’,5’-monophosphate, a membrane-permeable cGMP analog, restored LTD without TRH application. These results suggest that TRH is involved in cerebellar LTD presumably by upregulating the basal cGMP level in Purkinje cells, and, consequently, in motor learning. Frontiers Media S.A. 2018-12-12 /pmc/articles/PMC6299015/ /pubmed/30618637 http://dx.doi.org/10.3389/fncel.2018.00490 Text en Copyright © 2018 Watanave, Matsuzaki, Nakajima, Ozawa, Yamada and Hirai. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Watanave, Masashi Matsuzaki, Yasunori Nakajima, Yasuyo Ozawa, Atsushi Yamada, Masanobu Hirai, Hirokazu Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning |
title | Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning |
title_full | Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning |
title_fullStr | Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning |
title_full_unstemmed | Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning |
title_short | Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning |
title_sort | contribution of thyrotropin-releasing hormone to cerebellar long-term depression and motor learning |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6299015/ https://www.ncbi.nlm.nih.gov/pubmed/30618637 http://dx.doi.org/10.3389/fncel.2018.00490 |
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