Nigral dopamine loss induces a global upregulation of presynaptic dopamine D1 receptor facilitation of the striatonigral GABAergic output
| العنوان: | Nigral dopamine loss induces a global upregulation of presynaptic dopamine D1 receptor facilitation of the striatonigral GABAergic output |
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| المؤلفون: | Fu-Ming Zhou, Li Li, Shengyuan Ding |
| المصدر: | Journal of Neurophysiology. 113:1697-1711 |
| بيانات النشر: | American Physiological Society, 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Physiology, Dopamine, Substantia nigra, Striatum, Neural Circuits, Biology, Mice, Axon terminal, Basal ganglia, medicine, Animals, gamma-Aminobutyric Acid, Homeodomain Proteins, Receptors, Dopamine D1, General Neuroscience, Ventral striatum, Up-Regulation, Substantia Nigra, Ventral tegmental area, medicine.anatomical_structure, nervous system, Synapses, GABAergic, Neuroscience, Transcription Factors, medicine.drug |
| الوصف: | In Parkinson's disease (PD), the dopamine (DA) neuron loss in the substantia nigra and the DA axon loss in the dorsal striatum are severe, but DA neurons in the ventral tegmental area and DA axons in middle and ventral striatal subregions are less affected. Severe DA loss leads to DA receptor supersensitivity, but it was not known whether the supersensitivity of the DA D1 receptors (D1Rs) on the striatonigral axon terminal is determined by the severe striatal or nigral DA loss. This question is important because these two possibilities affect the extent of the striatonigral terminals with supersensitive D1Rs and hence the strength of the direct pathway output. Here we have investigated this question in the transcription factor Pitx3 mutant mice that have a PD-like DA loss pattern. We found that the presynaptic D1R function was upregulated globally: the D1R-mediated facilitation was equally enhanced for the striatonigral GABA output originated in the dorsal striatum where the DA loss is severe and the somatic D1Rs are supersensitive, and for the striatonigral GABA output originated in the middle and ventral striatum where the DA loss is moderate and the somatic D1Rs are not supersensitive. These results suggest that severe nigral DA loss is sufficient to induce functional upregulation of the D1Rs on striatonigral axon terminals. Consequently, in PD, the globally enhanced D1Rs on striatonigral axon terminals originated in broad striatal subregions may strongly enhance the striatonigral GABA output upon D1R stimulation, potentially contributing to D1R agonism's profound motor-stimulating effects. |
| تدمد: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.00752.2014 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::70871af8defdff2a9fc9f79655d2658f https://doi.org/10.1152/jn.00752.2014 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....70871af8defdff2a9fc9f79655d2658f |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221598 00223077 |
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| DOI: | 10.1152/jn.00752.2014 |