title: Abnormal plasticity in dystonia: Disruption of synaptic homeostasis.
abstract: Work over the past two decades lead to substantial changes in our understanding of dystonia, which was, until recently, considered an exclusively sporadic movement disorder. The discovery of several gene mutations responsible for many inherited forms of dystonia has prompted much effort in the generation of transgenic mouse models bearing mutations found in patients. The large majority of these rodent models do not exhibit overt phenotypic abnormalities, or neuronal loss in specific brain areas. Nevertheless, both subtle motor abnormalities and significant alterations of synaptic plasticity have been recorded in mice, suggestive of an altered basal ganglia circuitry. In addition, robust evidence from experimental and clinical work supports the assumption that dystonia may indeed be considered a disorder linked to the disruption of synaptic "scaling", with a prevailing facilitation of synaptic potentiation, together with the loss of synaptic inhibitory processes. Notably, neurophysiological studies from patients carrying gene mutations as well as from non-manifesting carriers have shown the presence of synaptic plasticity abnormalities, indicating the presence of specific endophenotypic traits in carriers of the gene mutation. In this survey, we review findings from a broad range of data, obtained both from animal models and human research, and propose that the abnormalities of synaptic plasticity described in mice and humans may be considered an endophenotype to dystonia, and a valid and powerful tool to investigate the pathogenic mechanisms underlying this movement disorder. This article is part of a Special Issue entitled "Advances in dystonia".
authors.affiliation: Department of Neuroscience, Psychiatry and Anesthesiological Sciences, University of Messina, Italy.
authors.forename: Angelo
authors.initials: A
authors.lastname: Quartarone
authors.forename: Antonio
authors.initials: A
authors.lastname: Pisani
mesh_terms: D000818:Animals; D004421:Dystonia / Q000235:genetics / Q000473:pathology / Q000503:physiopathology; D020821:Dystonic Disorders / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D006706:Homeostasis; D006801:Humans; D051379:Mice; D009473:Neuronal Plasticity / Q000502:physiology*; D013569:Synapses / Q000473:pathology*