Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning
Summary: Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder that often presents with psychiatric conditions, including autism spectrum disorder (ASD). ASD is characterized by restricted, repetitive, and inflexible behaviors, which may result from abnormal activity in striatal circuits...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-08-01
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| Series: | Cell Reports |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124721009414 |
| _version_ | 1818367910118162432 |
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| author | Katelyn N. Benthall Katherine R. Cording Alexander H.C.W. Agopyan-Miu Corinna D. Wong Emily Y. Chen Helen S. Bateup |
| author_facet | Katelyn N. Benthall Katherine R. Cording Alexander H.C.W. Agopyan-Miu Corinna D. Wong Emily Y. Chen Helen S. Bateup |
| author_sort | Katelyn N. Benthall |
| collection | DOAJ |
| description | Summary: Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder that often presents with psychiatric conditions, including autism spectrum disorder (ASD). ASD is characterized by restricted, repetitive, and inflexible behaviors, which may result from abnormal activity in striatal circuits that mediate motor learning and action selection. To test whether altered striatal activity contributes to aberrant motor behaviors in the context of TSC, we conditionally deleted Tsc1 from direct or indirect pathway striatal projection neurons (dSPNs or iSPNs, respectively). We find that dSPN-specific loss of Tsc1 impairs endocannabinoid-mediated long-term depression (eCB-LTD) at cortico-dSPN synapses and strongly enhances corticostriatal synaptic drive, which is not observed in iSPNs. dSPN-Tsc1 KO, but not iSPN-Tsc1 KO, mice show enhanced motor learning, a phenotype observed in several mouse models of ASD. These findings demonstrate that dSPNs are particularly sensitive to Tsc1 loss and suggest that enhanced corticostriatal activation may contribute to altered motor behaviors in TSC. |
| first_indexed | 2024-12-13T22:59:33Z |
| format | Article |
| id | doaj.art-b1d627606e414e55bdf47e0a7c6163f6 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T22:59:33Z |
| publishDate | 2021-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-b1d627606e414e55bdf47e0a7c6163f62022-12-21T23:28:25ZengElsevierCell Reports2211-12472021-08-01366109511Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learningKatelyn N. Benthall0Katherine R. Cording1Alexander H.C.W. Agopyan-Miu2Corinna D. Wong3Emily Y. Chen4Helen S. Bateup5Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USAHelen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USADepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USADepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USADepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USADepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA 94720, USA; Helen Wills Neuroscience Institute, University of California, Berkeley, Berkeley, CA 94720, USA; Chan Zuckerberg Biohub, San Francisco, CA 94158, USA; Corresponding authorSummary: Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder that often presents with psychiatric conditions, including autism spectrum disorder (ASD). ASD is characterized by restricted, repetitive, and inflexible behaviors, which may result from abnormal activity in striatal circuits that mediate motor learning and action selection. To test whether altered striatal activity contributes to aberrant motor behaviors in the context of TSC, we conditionally deleted Tsc1 from direct or indirect pathway striatal projection neurons (dSPNs or iSPNs, respectively). We find that dSPN-specific loss of Tsc1 impairs endocannabinoid-mediated long-term depression (eCB-LTD) at cortico-dSPN synapses and strongly enhances corticostriatal synaptic drive, which is not observed in iSPNs. dSPN-Tsc1 KO, but not iSPN-Tsc1 KO, mice show enhanced motor learning, a phenotype observed in several mouse models of ASD. These findings demonstrate that dSPNs are particularly sensitive to Tsc1 loss and suggest that enhanced corticostriatal activation may contribute to altered motor behaviors in TSC.http://www.sciencedirect.com/science/article/pii/S2211124721009414Tuberous Sclerosis ComplexTsc1Tsc2striatumdirect pathwayindirect pathway |
| spellingShingle | Katelyn N. Benthall Katherine R. Cording Alexander H.C.W. Agopyan-Miu Corinna D. Wong Emily Y. Chen Helen S. Bateup Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning Cell Reports Tuberous Sclerosis Complex Tsc1 Tsc2 striatum direct pathway indirect pathway |
| title | Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning |
| title_full | Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning |
| title_fullStr | Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning |
| title_full_unstemmed | Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning |
| title_short | Loss of Tsc1 from striatal direct pathway neurons impairs endocannabinoid-LTD and enhances motor routine learning |
| title_sort | loss of tsc1 from striatal direct pathway neurons impairs endocannabinoid ltd and enhances motor routine learning |
| topic | Tuberous Sclerosis Complex Tsc1 Tsc2 striatum direct pathway indirect pathway |
| url | http://www.sciencedirect.com/science/article/pii/S2211124721009414 |
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