Synaptic plasticity in the caudate nucleus of patients with Parkinson's disease

Abstract

The loss of dopaminergic neurons from the substantia nigra in Parkinson's disease (PD) may provoke a reorganization of cellular interactions in the nigrostriatal pathway. Indeed, a plasticity of putative corticostriatal synapses has been evidenced in the striatum of rats with a 6-hydroxy-dopamine-induced lesion of the substantia nigra. However, to our knowledge, synaptic plasticity in the striatum has not previously been investigated in human PD. In this study, we have analysed, at electron microscope level, the morphological characteristics of the synapses formed by afferents in asymmetric contact with dendritic spines of neurons in the caudate nucleus of three patients with PD and three matched controls. The length of the postsynaptic densities and the number of perforated synapses were both significantly increased (24 and 88%, respectively) in the PD patients; the size of these afferents and the surface area occupied by their mitochondria also showed an increase (24 and 50%, respectively), although not statistically significant. The size and density of dendritic spines and the size of postsynaptic density perforations were unchanged. These data indicate the presence of plasticity of the putative corticostriatal synapses in PD and suggest a hyperactivity of cortical afferents to GABAergic neurons.