NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control.
The striatum plays a fundamental role in motor learning and reward-related behaviors that are synergistically shaped by populations of D1 dopamine receptor (D1R)- and D2 dopamine receptor (D2R)-expressing medium spiny neurons (MSNs). How various neurotransmitter inputs converging on common intracell...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2019-10-01
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| Series: | PLoS Biology |
| Online Access: | https://doi.org/10.1371/journal.pbio.3000477 |
| _version_ | 1818578246231392256 |
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| author | Laurie P Sutton Brian S Muntean Olga Ostrovskaya Stefano Zucca Maria Dao Cesare Orlandi Chenghui Song Keqiang Xie Kirill A Martemyanov |
| author_facet | Laurie P Sutton Brian S Muntean Olga Ostrovskaya Stefano Zucca Maria Dao Cesare Orlandi Chenghui Song Keqiang Xie Kirill A Martemyanov |
| author_sort | Laurie P Sutton |
| collection | DOAJ |
| description | The striatum plays a fundamental role in motor learning and reward-related behaviors that are synergistically shaped by populations of D1 dopamine receptor (D1R)- and D2 dopamine receptor (D2R)-expressing medium spiny neurons (MSNs). How various neurotransmitter inputs converging on common intracellular pathways are parsed out to regulate distinct behavioral outcomes in a neuron-specific manner is poorly understood. Here, we reveal that distinct contributions of D1R-MSNs and D2R-MSNs towards reward and motor behaviors are delineated by the multifaceted signaling protein neurofibromin 1 (NF1). Using genetic mouse models, we show that NF1 in D1R-MSN modulates opioid reward, whereas loss of NF1 in D2R-MSNs delays motor learning by impeding the formation and consolidation of repetitive motor sequences. We found that motor learning deficits upon NF1 loss were associated with the disruption in dopamine signaling to cAMP in D2R-MSN. Restoration of cAMP levels pharmacologically or chemogenetically rescued the motor learning deficits seen upon NF1 loss in D2R-MSN. Our findings illustrate that multiplex signaling capabilities of MSNs are deployed at the level of intracellular pathways to achieve cell-specific control over behavioral outcomes. |
| first_indexed | 2024-12-16T06:42:45Z |
| format | Article |
| id | doaj.art-aa11db4ea136455e9a462b928d2d5b88 |
| institution | Directory Open Access Journal |
| issn | 1544-9173 1545-7885 |
| language | English |
| last_indexed | 2024-12-16T06:42:45Z |
| publishDate | 2019-10-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj.art-aa11db4ea136455e9a462b928d2d5b882022-12-21T22:40:39ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852019-10-011710e300047710.1371/journal.pbio.3000477NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control.Laurie P SuttonBrian S MunteanOlga OstrovskayaStefano ZuccaMaria DaoCesare OrlandiChenghui SongKeqiang XieKirill A MartemyanovThe striatum plays a fundamental role in motor learning and reward-related behaviors that are synergistically shaped by populations of D1 dopamine receptor (D1R)- and D2 dopamine receptor (D2R)-expressing medium spiny neurons (MSNs). How various neurotransmitter inputs converging on common intracellular pathways are parsed out to regulate distinct behavioral outcomes in a neuron-specific manner is poorly understood. Here, we reveal that distinct contributions of D1R-MSNs and D2R-MSNs towards reward and motor behaviors are delineated by the multifaceted signaling protein neurofibromin 1 (NF1). Using genetic mouse models, we show that NF1 in D1R-MSN modulates opioid reward, whereas loss of NF1 in D2R-MSNs delays motor learning by impeding the formation and consolidation of repetitive motor sequences. We found that motor learning deficits upon NF1 loss were associated with the disruption in dopamine signaling to cAMP in D2R-MSN. Restoration of cAMP levels pharmacologically or chemogenetically rescued the motor learning deficits seen upon NF1 loss in D2R-MSN. Our findings illustrate that multiplex signaling capabilities of MSNs are deployed at the level of intracellular pathways to achieve cell-specific control over behavioral outcomes.https://doi.org/10.1371/journal.pbio.3000477 |
| spellingShingle | Laurie P Sutton Brian S Muntean Olga Ostrovskaya Stefano Zucca Maria Dao Cesare Orlandi Chenghui Song Keqiang Xie Kirill A Martemyanov NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control. PLoS Biology |
| title | NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control. |
| title_full | NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control. |
| title_fullStr | NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control. |
| title_full_unstemmed | NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control. |
| title_short | NF1-cAMP signaling dissociates cell type-specific contributions of striatal medium spiny neurons to reward valuation and motor control. |
| title_sort | nf1 camp signaling dissociates cell type specific contributions of striatal medium spiny neurons to reward valuation and motor control |
| url | https://doi.org/10.1371/journal.pbio.3000477 |
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