Thalamic changes in Parkinson's disease.
One of the most marked differences to be identified in Parkinson's disease is the change in activity of thalamic neurons in the motor circuits. Because dopamine replacement therapies largely alleviate these motor circuit abnormalities, it has been assumed that pathology in the basal ganglia is entirely responsible for the aberrant thalamic activity which then permeates the motor circuits. However, there is considerable evidence that pathology in the thalamus itself contributes to the abnormal neural activity characteristic of Parkinson's disease. In a series of studies examining the degree of degeneration in the thalamus, we have observed selective degeneration in the intralaminar thalamic nuclei in patients with levodopa-responsive Parkinson's disease. The nuclei involved are the caudal intralaminar nuclei (the centre-median/parafascicular complex), the parataenial, cucullar and central lateral nuclei. The centre-median/parafascicular complex provides important glutaminergic feedback from the thalamus to the putamen and is a pathway that is greatly enlarged in primates. There is 30-40% loss in this region of the thalamus in idiopathic Parkinson's disease, with non-parvalbumin-containing neurons degenerating the most (70% average loss). Our recent work suggests that the preservation of this pathway may contribute to dystonia in Parkinson's disease. The central lateral and cucullar thalamic nuclei degenerate 30-50%, while the parataenial nucleus sustains a 55% loss of neurons in association with significant alpha-synuclein deposition which correlates with disease duration. Damage to these regions appears to impact on cognition, awareness and perception. These studies suggest that direct thalamic pathology contributes to the symptoms of Parkinson's disease.
Halliday
Glenda M
GM
Prince of Wales Medical Research Institute and University of New South Wales, Sydney, Australia. g.halliday@powmri.edu.au
D000818:Animals; D006801:Humans; D009415:Nerve Net / Q000473:pathology / Q000503:physiopathology; D009434:Neural Pathways / Q000473:pathology / Q000503:physiopathology; D009474:Neurons / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology*; D013788:Thalamus / Q000473:pathology*; D051844:alpha-Synuclein / Q000378:metabolism
D051844:alpha-Synuclein