Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA
A major physiologic sign in Parkinson disease is the occurrence of abnormal oscillations in cortico-basal ganglia circuits, which can be normalized by l-DOPA therapy. Under normal circumstances, oscillatory activity in these circuits is modulated as behaviors are learned and performed, but how dopam...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | en_US |
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National Academy of Sciences (U.S.)
2013
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| Online Access: | http://hdl.handle.net/1721.1/78873 https://orcid.org/0000-0001-9197-7711 https://orcid.org/0000-0003-2381-0834 https://orcid.org/0000-0002-4326-7720 |
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| author | Lemaire, Nune Ledia, F. Hernandez Hu, Dan Kubota, Yasuo Howe, Mark William Graybiel, Ann M. |
| author2 | McGovern Institute for Brain Research at MIT |
| author_facet | McGovern Institute for Brain Research at MIT Lemaire, Nune Ledia, F. Hernandez Hu, Dan Kubota, Yasuo Howe, Mark William Graybiel, Ann M. |
| author_sort | Lemaire, Nune |
| collection | MIT |
| description | A major physiologic sign in Parkinson disease is the occurrence of abnormal oscillations in cortico-basal ganglia circuits, which can be normalized by l-DOPA therapy. Under normal circumstances, oscillatory activity in these circuits is modulated as behaviors are learned and performed, but how dopamine depletion affects such modulation is not yet known. We here induced unilateral dopamine depletion in the sensorimotor striatum of rats and then recorded local field potential (LFP) activity in the dopamine-depleted region and its contralateral correspondent as we trained the rats on a conditional T-maze task. Unexpectedly, the dopamine depletion had little effect on oscillations recorded in the pretask baseline period. Instead, the depletion amplified oscillations across delta (∼3 Hz), theta (∼8 Hz), beta (∼13 Hz), and low-gamma (∼48 Hz) ranges selectively during task performance times when each frequency band was most strongly modulated, and only after extensive training had occurred. High-gamma activity (65–100 Hz), in contrast, was weakened independent of task time or learning stage. The depletion also increased spike-field coupling of fast-spiking interneurons to low-gamma oscillations. l-DOPA therapy normalized all of these effects except those at low gamma. Our findings suggest that the task-related and learning-related dynamics of LFP oscillations are the primary targets of dopamine depletion, resulting in overexpression of behaviorally relevant oscillations. l-DOPA normalizes these dynamics except at low-gamma, linked by spike-field coupling to fast-spiking interneurons, now known to undergo structural changes after dopamine depletion and to lack normalization of spike activity following l-DOPA therapy. |
| first_indexed | 2024-09-23T09:42:43Z |
| format | Article |
| id | mit-1721.1/78873 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T09:42:43Z |
| publishDate | 2013 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/788732022-09-26T13:17:40Z Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA Lemaire, Nune Ledia, F. Hernandez Hu, Dan Kubota, Yasuo Howe, Mark William Graybiel, Ann M. McGovern Institute for Brain Research at MIT Lemaire, Nune Ledia, F. Hernandez Hu, Dan Kubota, Yasuo Howe, Mark William Graybiel, Ann M. A major physiologic sign in Parkinson disease is the occurrence of abnormal oscillations in cortico-basal ganglia circuits, which can be normalized by l-DOPA therapy. Under normal circumstances, oscillatory activity in these circuits is modulated as behaviors are learned and performed, but how dopamine depletion affects such modulation is not yet known. We here induced unilateral dopamine depletion in the sensorimotor striatum of rats and then recorded local field potential (LFP) activity in the dopamine-depleted region and its contralateral correspondent as we trained the rats on a conditional T-maze task. Unexpectedly, the dopamine depletion had little effect on oscillations recorded in the pretask baseline period. Instead, the depletion amplified oscillations across delta (∼3 Hz), theta (∼8 Hz), beta (∼13 Hz), and low-gamma (∼48 Hz) ranges selectively during task performance times when each frequency band was most strongly modulated, and only after extensive training had occurred. High-gamma activity (65–100 Hz), in contrast, was weakened independent of task time or learning stage. The depletion also increased spike-field coupling of fast-spiking interneurons to low-gamma oscillations. l-DOPA therapy normalized all of these effects except those at low gamma. Our findings suggest that the task-related and learning-related dynamics of LFP oscillations are the primary targets of dopamine depletion, resulting in overexpression of behaviorally relevant oscillations. l-DOPA normalizes these dynamics except at low-gamma, linked by spike-field coupling to fast-spiking interneurons, now known to undergo structural changes after dopamine depletion and to lack normalization of spike activity following l-DOPA therapy. National Institutes of Health (U.S.) (National Institute of Neurological Disorders and Stroke P50 NS-38372) National Parkinson Foundation (U.S.) (Parkinson’s Disease Foundation Fellowship) National Institutes of Health (U.S.) (Graduate Student Fellowship) Stanley H. and Sheila G. Sydney Fund 2013-05-14T13:40:08Z 2013-05-14T13:40:08Z 2012-10 Article http://purl.org/eprint/type/JournalArticle 0027-8424 1091-6490 http://hdl.handle.net/1721.1/78873 Lemaire, N., L. F. Hernandez, D. Hu, et al. Effects of Dopamine Depletion on LFP Oscillations in Striatum Are Task- and Learning-dependent and Selectively Reversed by L-DOPA. Proceedings of the National Academy of Sciences 109(44): 18126–18131, 2012. https://orcid.org/0000-0001-9197-7711 https://orcid.org/0000-0003-2381-0834 https://orcid.org/0000-0002-4326-7720 en_US http://dx.doi.org/10.1073/pnas.1216403109 Proceedings of the National Academy of Sciences of the United States of America Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) PNAS |
| spellingShingle | Lemaire, Nune Ledia, F. Hernandez Hu, Dan Kubota, Yasuo Howe, Mark William Graybiel, Ann M. Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA |
| title | Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA |
| title_full | Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA |
| title_fullStr | Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA |
| title_full_unstemmed | Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA |
| title_short | Effects of dopamine depletion on LFP oscillations in striatum are task- and learning-dependent and selectively reversed by l-DOPA |
| title_sort | effects of dopamine depletion on lfp oscillations in striatum are task and learning dependent and selectively reversed by l dopa |
| url | http://hdl.handle.net/1721.1/78873 https://orcid.org/0000-0001-9197-7711 https://orcid.org/0000-0003-2381-0834 https://orcid.org/0000-0002-4326-7720 |
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