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The basal ganglia in Parkinson disease. The primary defect is destruction of the dopaminergic neurons of the SNpc. The striatal neurons that form the direct pathway from the striatum to the SNpr and GPi express primarily the excitatory D1 DA receptor, whereas the striatal neurons that project to the GPe and form the indirect pathway express the inhibitory D2 dopamine receptor. Thus, loss of the dopaminergic input to the striatum has a differential effect on the two outflow pathways; the direct pathway to the SNpr and GPi is less active (structures in purple), whereas the activity in the indirect pathway is increased (structures in red). The net effect is that neurons in the SNpr and GPi become more active. This leads to increased inhibition of the VA/VL thalamus and reduced excitatory input to the cortex. Light blue lines indicate primary pathways with reduced activity. (See legend to Figure 22–2 for Source: Treatment of Central Nervous System Degenerative Disorders, Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e definitions of anatomical abbreviations.) Citation: Brunton LL, Chabner BA, Knollmann BC. Goodman & Gilman's: The Pharmacological Basis of Therapeutics, 12e; 2011 Available at: http://mhmedical.com/ Accessed: May 11, 2017 Copyright © 2017 McGraw-Hill Education. All rights reserved