Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia
Levodopa-induced dyskinesia (LID) is a major complication of long-term dopamine replacement therapy for Parkinson's disease, and becomes increasingly problematic in the advanced stage of the disease. Although the cause of LID still remains unclear, there is accumulating evidence from animal exp...
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| Format: | Article |
| Language: | English |
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Elsevier
2014-04-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996113003586 |
| _version_ | 1819159825821466624 |
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| author | Tatsuya Ueno Junko Yamada Haruo Nishijima Akira Arai Keisuke Migita Masayuki Baba Shinya Ueno Masahiko Tomiyama |
| author_facet | Tatsuya Ueno Junko Yamada Haruo Nishijima Akira Arai Keisuke Migita Masayuki Baba Shinya Ueno Masahiko Tomiyama |
| author_sort | Tatsuya Ueno |
| collection | DOAJ |
| description | Levodopa-induced dyskinesia (LID) is a major complication of long-term dopamine replacement therapy for Parkinson's disease, and becomes increasingly problematic in the advanced stage of the disease. Although the cause of LID still remains unclear, there is accumulating evidence from animal experiments that it results from maladaptive plasticity, resulting in supersensitive excitatory transmission at corticostriatal synapses. Recent work using transcranial magnetic stimulation suggests that the motor cortex displays the same supersensitivity in Parkinson's disease patients with LID. To date, the cellular mechanisms underlying the abnormal cortical plasticity have not been examined. The morphology of the dendritic spines has a strong relationship to synaptic plasticity. Therefore, we explored the spine morphology of pyramidal neurons in the motor cortex in a rat model of LID. We used control rats, 6-hydroxydopamine-lesioned rats (a model of Parkinson's disease), 6-hydroxydopamine-lesioned rats chronically treated with levodopa (a model of LID), and control rats chronically treated with levodopa. Because the direct pathway of the basal ganglia plays a central role in the development of LID, we quantified the density and size of dendritic spines in intratelencephalic (IT)-type pyramidal neurons in M1 cortex that project to the striatal medium spiny neurons in the direct pathway. The spine density was not different among the four groups. In contrast, spine size became enlarged in the Parkinson's disease and LID rat models. The enlargement was significantly greater in the LID model than in the Parkinson's disease model. This enlargement of the spines suggests that IT-type pyramidal neurons acquire supersensitivity to excitatory stimuli. To confirm this possibility, we monitored miniature excitatory postsynaptic currents (mEPSCs) in the IT-type pyramidal neurons in M1 cortex using whole-cell patch clamp. The amplitude of the mEPSCs was significantly increased in the LID model compared with the control. This indicates that the IT-type pyramidal neurons become hyperexcited in the LID model, paralleling the enlargement of spines. Thus, spine enlargement and the resultant hyperexcitability of IT-type pyramidal neurons in M1 cortex might contribute to the abnormal cortical neuronal plasticity in LID. |
| first_indexed | 2024-12-22T16:46:43Z |
| format | Article |
| id | doaj.art-1251116e9b7b460985f594a47a9e3113 |
| institution | Directory Open Access Journal |
| issn | 1095-953X |
| language | English |
| last_indexed | 2024-12-22T16:46:43Z |
| publishDate | 2014-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj.art-1251116e9b7b460985f594a47a9e31132022-12-21T18:19:42ZengElsevierNeurobiology of Disease1095-953X2014-04-0164142149Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesiaTatsuya Ueno0Junko Yamada1Haruo Nishijima2Akira Arai3Keisuke Migita4Masayuki Baba5Shinya Ueno6Masahiko Tomiyama7Department of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan; Department of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, Japan; Corresponding author at: Department of Neurology, Aomori Prefectural Central Hospital, 2-1-1 Higashi-Tsukurimichi, Aomori 030-8551, Japan. Fax: +81 17 726 1885.Department of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, JapanDepartment of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan; Department of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, JapanDepartment of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan; Department of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, JapanDepartment of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, JapanDepartment of Neurology, Aomori Prefectural Central Hospital, Aomori, JapanDepartment of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, JapanDepartment of Neurology, Aomori Prefectural Central Hospital, Aomori, Japan; Department of Neurophysiology, Institute of Brain Science, Hirosaki University Graduate School of Medicine, Hirosaki, JapanLevodopa-induced dyskinesia (LID) is a major complication of long-term dopamine replacement therapy for Parkinson's disease, and becomes increasingly problematic in the advanced stage of the disease. Although the cause of LID still remains unclear, there is accumulating evidence from animal experiments that it results from maladaptive plasticity, resulting in supersensitive excitatory transmission at corticostriatal synapses. Recent work using transcranial magnetic stimulation suggests that the motor cortex displays the same supersensitivity in Parkinson's disease patients with LID. To date, the cellular mechanisms underlying the abnormal cortical plasticity have not been examined. The morphology of the dendritic spines has a strong relationship to synaptic plasticity. Therefore, we explored the spine morphology of pyramidal neurons in the motor cortex in a rat model of LID. We used control rats, 6-hydroxydopamine-lesioned rats (a model of Parkinson's disease), 6-hydroxydopamine-lesioned rats chronically treated with levodopa (a model of LID), and control rats chronically treated with levodopa. Because the direct pathway of the basal ganglia plays a central role in the development of LID, we quantified the density and size of dendritic spines in intratelencephalic (IT)-type pyramidal neurons in M1 cortex that project to the striatal medium spiny neurons in the direct pathway. The spine density was not different among the four groups. In contrast, spine size became enlarged in the Parkinson's disease and LID rat models. The enlargement was significantly greater in the LID model than in the Parkinson's disease model. This enlargement of the spines suggests that IT-type pyramidal neurons acquire supersensitivity to excitatory stimuli. To confirm this possibility, we monitored miniature excitatory postsynaptic currents (mEPSCs) in the IT-type pyramidal neurons in M1 cortex using whole-cell patch clamp. The amplitude of the mEPSCs was significantly increased in the LID model compared with the control. This indicates that the IT-type pyramidal neurons become hyperexcited in the LID model, paralleling the enlargement of spines. Thus, spine enlargement and the resultant hyperexcitability of IT-type pyramidal neurons in M1 cortex might contribute to the abnormal cortical neuronal plasticity in LID.http://www.sciencedirect.com/science/article/pii/S0969996113003586Parkinson's diseaseDyskinesiaLevodopaMotor cortexSpinePlasticity |
| spellingShingle | Tatsuya Ueno Junko Yamada Haruo Nishijima Akira Arai Keisuke Migita Masayuki Baba Shinya Ueno Masahiko Tomiyama Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia Neurobiology of Disease Parkinson's disease Dyskinesia Levodopa Motor cortex Spine Plasticity |
| title | Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia |
| title_full | Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia |
| title_fullStr | Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia |
| title_full_unstemmed | Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia |
| title_short | Morphological and electrophysiological changes in intratelencephalic-type pyramidal neurons in the motor cortex of a rat model of levodopa-induced dyskinesia |
| title_sort | morphological and electrophysiological changes in intratelencephalic type pyramidal neurons in the motor cortex of a rat model of levodopa induced dyskinesia |
| topic | Parkinson's disease Dyskinesia Levodopa Motor cortex Spine Plasticity |
| url | http://www.sciencedirect.com/science/article/pii/S0969996113003586 |
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