Reconsideration of the firing loop models for dystonia and Parkinson's disease. Issue 1 (11th October 2022)

• Record Type: Journal Article
• Authors: Yokoi, Fumiaki
• Is Part Of: Neurology and clinical neuroscience. Volume 11:Issue 1(2023)
• Page Start: 3
• Page End: 9
• Publication Date: 2022-10-11
• Subjects: dopamine -- dystonia -- firing loop model -- Parkinson's disease -- thalamic switch; Neurology -- Periodicals; Neurosciences -- Periodicals; 616.8
• DOI: 10.1111/ncn3.12670
• Languages: English
• ISSNs: 2049-4173

Abstract

Abstract: Parkinson's disease (PD) is a hypokinetic movement disorder with degeneration of dopaminergic and other neurons, whereas dystonia is a hyperkinetic movement disorder caused by various pathogenesis, that is, sporadic, genetic, stroke, brain injury, and other diseases, such as PD. Dopamine receptor 1 (D1R) antagonist and dopamine receptor 2 (D2R) antagonist induce dystonic symptom in monkey. Consistently, D1R antagonist and D2R antagonist decrease locomotion in mice. Moreover, D1R knock‐out (KO) mice and D2R KO mice show motor deficits. In humans, dopa‐responsive dystonia (DRD) is caused by genetically defective dopamine (DA) synthesis. DYT1 dystonia and genetic mouse models show decreased striatal D1R and D2R. Therefore, PD, pharmacological dystonia models, DRD and DYT1 dystonia, have defective DA pathways. Firing of globus pallidus internus (GPi) neurons is increased in PD and dystonia with local anesthesia. However, the ordinary firing loop model cannot explain how defective DA pathways induce dystonia. PD shows thalamic neurodegeneration, whereas PD with dystonia has relatively intact thalamic neurons. Since thalamic GABAergic interneurons are innervated by GPi GABAergic neurons, here I propose to add thalamic GABAergic interneurons between GPi GABAergic neurons and thalamic glutamatergic neurons as thalamic inverse pathway for healthy condition and dystonia, whereas thalamic ordinary pathway due to degeneration of thalamic GABAergic interneurons is suitable to PD. On the contrary, PD with dystonia has both thalamic ordinary and inverse pathways. Although precise thalamic circuits have not been elucidated, discrepancy in the ordinary firing loop model for dystonia seems to be solved by the thalamic switch from dystonia to PD.