Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice
Corticotropin-releasing factor (CRF) is a major neuromodulator that modulates cerebellar neuronal activity via CRF receptors during stress responses. In the cerebellar cortex, CRF dose-dependently increases the simple spike (SS) firing rate of Purkinje cells (PCs), while the synaptic mechanisms of t...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-07-01
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| Series: | Frontiers in Cellular Neuroscience |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fncel.2018.00184/full |
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| author | Hong-Wei Wang Hong-Wei Wang Jing-Tong Zhao Jing-Tong Zhao Bing-Xue Li Bing-Xue Li Shan-Shan Su Shan-Shan Su Yan-Hua Bing Yan-Hua Bing Chun-Ping Chu Wei-Ming Wang Yu-Zi Li De-Lai Qiu De-Lai Qiu De-Lai Qiu |
| author_facet | Hong-Wei Wang Hong-Wei Wang Jing-Tong Zhao Jing-Tong Zhao Bing-Xue Li Bing-Xue Li Shan-Shan Su Shan-Shan Su Yan-Hua Bing Yan-Hua Bing Chun-Ping Chu Wei-Ming Wang Yu-Zi Li De-Lai Qiu De-Lai Qiu De-Lai Qiu |
| author_sort | Hong-Wei Wang |
| collection | DOAJ |
| description | Corticotropin-releasing factor (CRF) is a major neuromodulator that modulates cerebellar neuronal activity via CRF receptors during stress responses. In the cerebellar cortex, CRF dose-dependently increases the simple spike (SS) firing rate of Purkinje cells (PCs), while the synaptic mechanisms of this are still unclear. We here investigated the effect of CRF on the spontaneous SS activity of cerebellar PCs in urethane-anesthetized mice by in vivo electrophysiological recording and pharmacological methods. Cell-attached recordings from PCs showed that micro-application of CRF in cerebellar cortical molecular layer induced a dose-dependent increase in SS firing rate in the absence of GABAA receptor activity. The CRF-induced increase in SS firing rate was completely blocked by a nonselective CRF receptor antagonist, α-helical CRF-(9–14). Nevertheless, application of either a selective CRF-R1 antagonist, BMS-763534 (BMS, 200 nM) or a selective CRF-R2 antagonist, antisauvagine-30 (200 nM) significantly attenuated, but failed to abolished the CRF-induced increase in PCs SS firing rate. In vivo whole-cell patch-clamp recordings from PCs showed that molecular layer application of CRF significantly increased the frequency, but not amplitude, of miniature postsynaptic currents (mEPSCs). The CRF-induced increase in the frequency of mEPSCs was abolished by a CRF-R2 antagonist, as well as protein kinase A (PKA) inhibitors. These results suggested that CRF acted on presynaptic CRF-R2 of cerebellar PCs resulting in an increase of glutamate release through PKA signaling pathway, which contributed to modulation of the cerebellar PCs outputs in Vivo in mice. |
| first_indexed | 2024-04-12T08:57:06Z |
| format | Article |
| id | doaj.art-83bf6c094f004f7ca5c2fb5cd094b369 |
| institution | Directory Open Access Journal |
| issn | 1662-5102 |
| language | English |
| last_indexed | 2024-04-12T08:57:06Z |
| publishDate | 2018-07-01 |
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| series | Frontiers in Cellular Neuroscience |
| spelling | doaj.art-83bf6c094f004f7ca5c2fb5cd094b3692022-12-22T03:39:21ZengFrontiers Media S.A.Frontiers in Cellular Neuroscience1662-51022018-07-011210.3389/fncel.2018.00184360890Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in MiceHong-Wei Wang0Hong-Wei Wang1Jing-Tong Zhao2Jing-Tong Zhao3Bing-Xue Li4Bing-Xue Li5Shan-Shan Su6Shan-Shan Su7Yan-Hua Bing8Yan-Hua Bing9Chun-Ping Chu10Wei-Ming Wang11Yu-Zi Li12De-Lai Qiu13De-Lai Qiu14De-Lai Qiu15Department of Cardiology, Affiliated Zhongshan Hospital of Dalian University, Dalian, ChinaKey Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, ChinaKey Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, ChinaDepartment of Cardiology, Affiliated Hospital of Yanbian University, Yanji, ChinaKey Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, ChinaDepartment of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, ChinaKey Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, ChinaDepartment of Cardiology, Affiliated Hospital of Yanbian University, Yanji, ChinaKey Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, ChinaDepartment of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, ChinaKey Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, ChinaDepartment of Osteology, Affiliated Zhongshan Hospital of Dalian University, Dalian, ChinaDepartment of Cardiology, Affiliated Hospital of Yanbian University, Yanji, ChinaKey Laboratory of Cellular Function and Pharmacology of Jilin Province, Yanbian University, Yanji, ChinaDepartment of Physiology and Pathophysiology, College of Medicine, Yanbian University, Yanji, ChinaKey Laboratory of Natural Resource of the Changbai Mountain and Functional Molecular of the Ministry of Education, Yanbian University, Yanji, ChinaCorticotropin-releasing factor (CRF) is a major neuromodulator that modulates cerebellar neuronal activity via CRF receptors during stress responses. In the cerebellar cortex, CRF dose-dependently increases the simple spike (SS) firing rate of Purkinje cells (PCs), while the synaptic mechanisms of this are still unclear. We here investigated the effect of CRF on the spontaneous SS activity of cerebellar PCs in urethane-anesthetized mice by in vivo electrophysiological recording and pharmacological methods. Cell-attached recordings from PCs showed that micro-application of CRF in cerebellar cortical molecular layer induced a dose-dependent increase in SS firing rate in the absence of GABAA receptor activity. The CRF-induced increase in SS firing rate was completely blocked by a nonselective CRF receptor antagonist, α-helical CRF-(9–14). Nevertheless, application of either a selective CRF-R1 antagonist, BMS-763534 (BMS, 200 nM) or a selective CRF-R2 antagonist, antisauvagine-30 (200 nM) significantly attenuated, but failed to abolished the CRF-induced increase in PCs SS firing rate. In vivo whole-cell patch-clamp recordings from PCs showed that molecular layer application of CRF significantly increased the frequency, but not amplitude, of miniature postsynaptic currents (mEPSCs). The CRF-induced increase in the frequency of mEPSCs was abolished by a CRF-R2 antagonist, as well as protein kinase A (PKA) inhibitors. These results suggested that CRF acted on presynaptic CRF-R2 of cerebellar PCs resulting in an increase of glutamate release through PKA signaling pathway, which contributed to modulation of the cerebellar PCs outputs in Vivo in mice.https://www.frontiersin.org/article/10.3389/fncel.2018.00184/fullcerebellar Purkinje cellin vivo whole-cell patch-clamp recordingcomplex spike (CS)corticotropin-releasing factor (CRF)miniature postsynaptic currentssimple-spike (SS) |
| spellingShingle | Hong-Wei Wang Hong-Wei Wang Jing-Tong Zhao Jing-Tong Zhao Bing-Xue Li Bing-Xue Li Shan-Shan Su Shan-Shan Su Yan-Hua Bing Yan-Hua Bing Chun-Ping Chu Wei-Ming Wang Yu-Zi Li De-Lai Qiu De-Lai Qiu De-Lai Qiu Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice Frontiers in Cellular Neuroscience cerebellar Purkinje cell in vivo whole-cell patch-clamp recording complex spike (CS) corticotropin-releasing factor (CRF) miniature postsynaptic currents simple-spike (SS) |
| title | Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice |
| title_full | Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice |
| title_fullStr | Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice |
| title_full_unstemmed | Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice |
| title_short | Corticotrophin-Releasing Factor Modulates Cerebellar Purkinje Cells Simple Spike Activity in Vivo in Mice |
| title_sort | corticotrophin releasing factor modulates cerebellar purkinje cells simple spike activity in vivo in mice |
| topic | cerebellar Purkinje cell in vivo whole-cell patch-clamp recording complex spike (CS) corticotropin-releasing factor (CRF) miniature postsynaptic currents simple-spike (SS) |
| url | https://www.frontiersin.org/article/10.3389/fncel.2018.00184/full |
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