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...
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Frontiers Media S.A.
2018-12-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00490/full |
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| author | Masashi Watanave Yasunori Matsuzaki Yasuyo Nakajima Atsushi Ozawa Masanobu Yamada Hirokazu Hirai Hirokazu Hirai |
| author_facet | Masashi Watanave Yasunori Matsuzaki Yasuyo Nakajima Atsushi Ozawa Masanobu Yamada Hirokazu Hirai Hirokazu Hirai |
| author_sort | Masashi Watanave |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-12-21T17:04:51Z |
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| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-12-21T17:04:51Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-2e9e0ce21f494d34af5ab49c564f2be22022-12-21T18:56:33ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-12-011210.3389/fncel.2018.00490423667Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor LearningMasashi Watanave0Yasunori Matsuzaki1Yasuyo Nakajima2Atsushi Ozawa3Masanobu Yamada4Hirokazu Hirai5Hirokazu Hirai6Department of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Medicine and Molecular Science, Gunma University Graduate School of Medicine, Maebashi, JapanDepartment of Neurophysiology and Neural Repair, Gunma University Graduate School of Medicine, Maebashi, JapanResearch Program for Neural Signalling, Division of Endocrinology, Metabolism and Signal Research, Gunma University Initiative for Advanced Research, Maebashi, JapanThyrotropin-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.https://www.frontiersin.org/article/10.3389/fncel.2018.00490/fullthyrotropin-releasing hormonemotor learningcerebellumLTDNO |
| spellingShingle | Masashi Watanave Yasunori Matsuzaki Yasuyo Nakajima Atsushi Ozawa Masanobu Yamada Hirokazu Hirai Hirokazu Hirai Contribution of Thyrotropin-Releasing Hormone to Cerebellar Long-Term Depression and Motor Learning Frontiers in Cellular Neuroscience thyrotropin-releasing hormone motor learning cerebellum LTD NO |
| 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 | thyrotropin-releasing hormone motor learning cerebellum LTD NO |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00490/full |
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