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 plasticity of corticostriatal synapses in Parkinson's disease (PD). The corticostriatal 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 afferent fibers making asymmetric contacts with the dendritic spines of neurons identified by D1R immunoreactivity, in the striatum of control subjects and PD patients. A quantitative analysis of the morphological characteristics of the synapses and of the number of perforated synapses (considered to be very active) was performed. In PD, a 50% increase in the number of perforated synapses making contact with D1R dendritic spines was observed, whereas no change in the number of perforated synapses on non-D1R spines was observed. The change in the number of perforated synapses on D1R dendrites was associated with a slight but nonsignificant increase in the surface area of the corticostriatal afferent fibers and the surface of the mitochondria in these fibers (+29.0% and +34.6%, respectively). This suggests a hyperactivity of corticostriatal fibers in contact with D1R-bearing neurons of the direct pathway in the basal ganglia circuitry. Since stimulation of the direct pathway is thought to alleviate the clinical symptoms of PD, this suggests that the differences observed may be involved in compensatory mechanisms.
Muriel
M P
MP
INSERM U 289, Experimental Neurology and Therapeutics, Hôpital de la Salpêtrière, 75013 Paris, France.
Agid
Y
Y
Hirsch
E
E
D000368:Aged; D000369:Aged, 80 and over; D001479:Basal Ganglia / Q000648:ultrastructure; D001921:Brain / Q000473:pathology; D016022:Case-Control Studies; D002421:Caudate Nucleus / Q000737:chemistry / Q000648:ultrastructure*; D003342:Corpus Striatum / Q000648:ultrastructure; D006801:Humans; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008854:Microscopy, Electron; D008875:Middle Aged; D009434:Neural Pathways; D009473:Neuronal Plasticity; D009475:Neurons, Afferent / Q000648:ultrastructure*; D010300:Parkinson Disease / Q000473:pathology*; D017447:Receptors, Dopamine D1 / Q000737:chemistry*; D013569:Synapses / Q000648:ultrastructure
D017447:Receptors, Dopamine D1