title: Cell type-specific plasticity of striatal projection neurons in parkinsonism and L-DOPA-induced dyskinesia.
abstract: The striatum is widely viewed as the fulcrum of pathophysiology in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). In these disease states, the balance in activity of striatal direct pathway spiny projection neurons (dSPNs) and indirect pathway spiny projection neurons (iSPNs) is disrupted, leading to aberrant action selection. However, it is unclear whether countervailing mechanisms are engaged in these states. Here we report that iSPN intrinsic excitability and excitatory corticostriatal synaptic connectivity were lower in PD models than normal; L-DOPA treatment restored these properties. Conversely, dSPN intrinsic excitability was elevated in tissue from PD models and suppressed in LID models. Although the synaptic connectivity of dSPNs did not change in PD models, it fell with L-DOPA treatment. In neither case, however, was the strength of corticostriatal connections globally scaled. Thus, SPNs manifested homeostatic adaptations in intrinsic excitability and in the number but not strength of excitatory corticostriatal synapses.
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department Experimental Medical Sciences, Lund University, Lund 22184, Sweden.
authors.forename: Tim
authors.initials: T
authors.lastname: Fieblinger
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Graves
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: Luke E
authors.initials: LE
authors.lastname: Sebel
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department Experimental Medical Sciences, Lund University, Lund 22184, Sweden.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alcacer
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: Joshua L
authors.initials: JL
authors.lastname: Plotkin
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: Tracy S
authors.initials: TS
authors.lastname: Gertler
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: C Savio
authors.initials: CS
authors.lastname: Chan
authors.affiliation: Picower Institute of Learning and Memory, Massachusetts Institute of Technology, Broad Institute of MIT and Harvard, Cambridge, Massachusetts 02139, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Heiman
authors.affiliation: Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, New York 10065, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Greengard
authors.affiliation: Basal Ganglia Pathophysiology Unit, Department Experimental Medical Sciences, Lund University, Lund 22184, Sweden.
authors.forename: M Angela
authors.initials: MA
authors.lastname: Cenci
authors.affiliation: Department of Physiology, Feinberg School of Medicine, Northwestern University, 303 East Chicago Avenue, Chicago, Illinois 60611, USA.
authors.forename: D James
authors.initials: DJ
authors.lastname: Surmeier
mesh_terms: D000818:Animals; D003342:Corpus Striatum / Q000503:physiopathology*; D049229:Dendritic Spines / Q000473:pathology; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000502:physiology*; D004409:Dyskinesia, Drug-Induced / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D008810:Mice, Inbred C57BL; D009473:Neuronal Plasticity; D020734:Parkinsonian Disorders / Q000473:pathology / Q000503:physiopathology*; D018091:Receptors, AMPA / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism
chemical_list: D018091:Receptors, AMPA; D016194:Receptors, N-Methyl-D-Aspartate