Plasticity of afferent fibers to striatal neurons bearing D1 dopamine receptors in Parkinson's disease

The loss of dopaminergic neurons in the substantia nigra provokes a plastic ity of corticostriatal synapses in Parkinson's disease (PD). The corticostr iatal pathway nevertheless makes synapses with neurons bearing D1 dopamine receptors (D1R) and/or D2 dopamine receptors. At the ultrastructural level, we analyzed the morphological characteristics of synapses formed by affere nt fibers making asymmetric contacts with the dendritic spines of neurons i dentified by D1R immunoreactivity, in the striatum of control subjects and PD patients. A quantitative analysis of the morphological characteristics o f the synapses and of the number of perforated synapses (considered to be v ery active) was performed. In PD, a 50% increase in the number of perforate d synapses making contact with DIR dendritic spines was observed, whereas n o change in the number of perforated synapses on non-D1R spines was observe d. The change in the number of perforated synapses on DIR dendrites was ass ociated with a slight but nonsignificant increase in the surface area of th e corticostriatal afferent fibers and the surface of the mitochondria in th ese fibers (+29.0% and +34.6%, respectively). This suggests a hyperactivity of corticostriatal fibers in contact with DIR-bearing neurons of the direc t pathway in the basal ganglia circuitry. Since stimulation of the direct p athway is thought to alleviate the clinical symptoms of PD, this suggests t hat the differences observed may be involved in compensatory mechanisms. (C ) 2001 Movement Disorder Society.