title: Plastic changes at corticostriatal synapses predict improved motor function in a partial lesion model of Parkinson's disease.
abstract: In Parkinson's disease, striatal dopamine depletion leads to plastic changes at excitatory corticostriatal and thalamostriatal synapses. The functional consequences of these responses on the expression of behavioral deficits are incompletely understood. In addition, most of the information on striatal synaptic plasticity has been obtained in models with severe striatal dopamine depletion, and less is known regarding changes during early stages of striatal denervation. Using a partial model of nigral cell loss based on intranigral injection of the proteasome inhibitor lactacystin, we demonstrate ultrastructural changes at corticostriatal synapses with a 15% increase in the length and 30% increase in the area of the postsynaptic densities at corticostriatal synapses 1 week following toxin administration. This increase was positively correlated with the performance of lactacystin-lesioned mice on the rotarod task, such that mice with a greater increase in the size of the postsynaptic density performed better on the rotarod task. We therefore propose that lengthening of the postsynaptic density at corticostriatal synapses acts as a compensatory mechanism to maintain motor function under conditions of partial dopamine depletion. The ultrastructure of thalamostriatal synapses remained unchanged following lactacystin administration. Our findings provide novel insights into the mechanisms of synaptic plasticity and behavioral compensation following partial loss of substantia nigra pars compacta neurons, such as those occurring during the early stages of Parkinson's disease.
authors.affiliation: Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Eduard
authors.initials: E
authors.lastname: Bentea
authors.affiliation: Research Services, Neurocytology Laboratory, Veterans Affairs Medical Center, Portland, OR, USA.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Moore
authors.affiliation: Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Lauren
authors.initials: L
authors.lastname: Deneyer
authors.affiliation: Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
authors.forename: Lise
authors.initials: L
authors.lastname: Verbruggen
authors.affiliation: Research Services, Neurocytology Laboratory, Veterans Affairs Medical Center, Portland, OR, USA.
authors.forename: Madeline J
authors.initials: MJ
authors.lastname: Churchill
authors.affiliation: Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Hood
authors.affiliation: Research Services, Neurocytology Laboratory, Veterans Affairs Medical Center, Portland, OR, USA; Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA.
authors.forename: Charles K
authors.initials: CK
authors.lastname: Meshul
authors.affiliation: Department of Pharmaceutical Biotechnology and Molecular Biology, Center for Neurosciences, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium. Electronic address: Ann.Massie@vub.ac.be.
authors.forename: Ann
authors.initials: A
authors.lastname: Massie
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage / Q000031:analogs & derivatives; D000818:Animals; D001522:Behavior, Animal; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D003342:Corpus Striatum / Q000187:drug effects / Q000503:physiopathology* / Q000648:ultrastructure; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D009434:Neural Pathways / Q000187:drug effects / Q000503:physiopathology / Q000648:ultrastructure; D009473:Neuronal Plasticity / Q000187:drug effects; D010300:Parkinson Disease / Q000473:pathology / Q000503:physiopathology*; D020734:Parkinsonian Disorders / Q000139:chemically induced; D065842:Pars Compacta / Q000187:drug effects; D057907:Post-Synaptic Density / Q000187:drug effects / Q000648:ultrastructure; D045442:Rotarod Performance Test; D013569:Synapses / Q000187:drug effects / Q000502:physiology* / Q000648:ultrastructure
chemical_list: C067713:lactacystin; D000111:Acetylcysteine
keywords: Compensation; Corticostriatal synapses; Partial dopamine depletion; Postsynaptic density; Synaptic plasticity; Thalamostriatal synapses