دورية أكاديمية
Excessive firing of dyskinesia-associated striatal direct pathway neurons is gated by dopamine and excitatory synaptic input.
| العنوان: | Excessive firing of dyskinesia-associated striatal direct pathway neurons is gated by dopamine and excitatory synaptic input. |
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| المؤلفون: | Ryan MB; Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, UCSF, San Francisco, CA 94158, USA; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Girasole AE; Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, UCSF, San Francisco, CA 94158, USA; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA., Flores AJ; Department of Neurosciences, UCSD, La Jolla, CA 92093, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA., Twedell EL; Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, UCSF, San Francisco, CA 94158, USA; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA., McGregor MM; Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, UCSF, San Francisco, CA 94158, USA; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA., Brakaj R; Department of Neurology, UCSF, San Francisco, CA 94158, USA., Paletzki RF; Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA., Hnasko TS; Department of Neurosciences, UCSD, La Jolla, CA 92093, USA; Veterans Affairs San Diego Healthcare System, San Diego, CA 92161, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA., Gerfen CR; Laboratory of Systems Neuroscience, National Institute of Mental Health, Bethesda, MD 20892, USA., Nelson AB; Neuroscience Graduate Program, UCSF, San Francisco, CA 94158, USA; Kavli Institute for Fundamental Neuroscience, UCSF, San Francisco, CA 94158, USA; Weill Institute for Neurosciences, UCSF, San Francisco, CA 94158, USA; Department of Neurology, UCSF, San Francisco, CA 94158, USA; Aligning Science Across Parkinson's (ASAP) Collaborative Research Network, Chevy Chase, MD 20815, USA. Electronic address: alexandra.nelson@ucsf.edu. |
| المصدر: | Cell reports [Cell Rep] 2024 Aug 27; Vol. 43 (8), pp. 114483. Date of Electronic Publication: 2024 Jul 17. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: United States NLM ID: 101573691 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2211-1247 (Electronic) NLM ISO Abbreviation: Cell Rep Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: [Cambridge, MA] : Cell Press, c 2012- |
| مواضيع طبية MeSH: | Dopamine*/metabolism , Levodopa*/pharmacology , Corpus Striatum*/metabolism , Corpus Striatum*/pathology , Neurons*/metabolism, Animals ; Mice ; Dyskinesia, Drug-Induced/metabolism ; Dyskinesia, Drug-Induced/pathology ; Synapses/metabolism ; Male ; Mice, Inbred C57BL ; Action Potentials/drug effects |
| مستخلص: | The striatum integrates dopaminergic and glutamatergic inputs to select preferred versus alternative actions. However, the precise mechanisms underlying this process remain unclear. One way to study action selection is to understand how it breaks down in pathological states. Here, we explored the cellular and synaptic mechanisms of levodopa-induced dyskinesia (LID), a complication of Parkinson's disease therapy characterized by involuntary movements. We used an activity-dependent tool (FosTRAP) in conjunction with a mouse model of LID to investigate functionally distinct subsets of striatal direct pathway medium spiny neurons (dMSNs). In vivo, levodopa differentially activates dyskinesia-associated (TRAPed) dMSNs compared to other dMSNs. We found this differential activation of TRAPed dMSNs is likely to be driven by higher dopamine receptor expression, dopamine-dependent excitability, and excitatory input from the motor cortex and thalamus. Together, these findings suggest how the intrinsic and synaptic properties of heterogeneous dMSN subpopulations integrate to support action selection. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2024. Published by Elsevier Inc.) |
| فهرسة مساهمة: | Keywords: CP: Neuroscience; Parkinson's Disease; basal ganglia; dopamine; dyskinesia; electrophysiology; levodopa; optogenetics; striatum |
| المشرفين على المادة: | VTD58H1Z2X (Dopamine) 46627O600J (Levodopa) |
| تواريخ الأحداث: | Date Created: 20240718 Date Completed: 20240830 Latest Revision: 20240831 |
| رمز التحديث: | 20240831 |
| DOI: | 10.1016/j.celrep.2024.114483 |
| PMID: | 39024096 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2211-1247 |
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| DOI: | 10.1016/j.celrep.2024.114483 |