title: Zooming in on the small: the plasticity of striatal dendritic spines in L-DOPA-induced dyskinesia.
abstract: The spiny dendrites of striatal projection neurons integrate synaptic inputs of different origins to regulate movement. It has long been known that these dendrites lose spines and display atrophic features in Parkinson's disease (PD), but the significance of these morphological changes has remained unknown. Some recent studies reveal a remarkable structural plasticity of striatal spines in parkinsonian rodents treated with L-3,4-dihydroxyphenylalanine (L-DOPA), and they demonstrate an association between this plasticity and the development of dyskinesia. These studies used different approaches and animal models, which possibly explains why they emphasize different plastic changes as being most closely linked to dyskinesia (such as a growth of new spines in neurons of the indirect pathway, or a loss of spines in neurons of the direct pathway, or the appearance of spines with aberrant synaptic features). Clearly, further investigations are required to reconcile these intriguing findings and integrate them in a coherent pathophysiological model. Nevertheless, these studies may mark the beginning of a new era for dyskinesia research. In addition to addressing neurochemical and molecular events that trigger involuntary movements, there is a need to better understand the long-lasting structural reorganization of cells and circuits that maintain the brain in a "dyskinesia-prone" state. This may lead to the identification of new efficacious approaches to prevent the complications of dopaminergic therapies in PD.
authors.affiliation: Basal Ganglia Pathophysiology Unit, Dept. Exp. Medical Science, Lund University, BMC F11, 221 84 Lund, Sweden.
authors.forename: Tim
authors.initials: T
authors.lastname: Fieblinger
authors.forename: M Angela
authors.initials: MA
authors.lastname: Cenci
mesh_terms: D000818:Animals; D000978:Antiparkinson Agents / Q000009:adverse effects; D003342:Corpus Striatum / Q000473:pathology*; D049229:Dendritic Spines / Q000187:drug effects / Q000473:pathology*; D004409:Dyskinesia, Drug-Induced / Q000209:etiology / Q000473:pathology*; D006801:Humans; D007980:Levodopa / Q000009:adverse effects; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure*
chemical_list: D000978:Antiparkinson Agents; D007980:Levodopa
keywords: Parkinson's disease; basal ganglia; cellular mechanisms; drug-induced movement disorders; striatum