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Plastic changes at corticostriatal synapses predict improved motor function in a partial lesion model of Parkinson's disease. / Bentea, Eduard Mihai; Moore, Cynthia; Deneyer, Lauren; Verbruggen, Lise; Churchill, Madeline J; Hood, Rebecca L; Meshul, Charles K; Massie, Ann.

In: Brain Research Bulletin, Vol. 130, 04.2017, p. 257-267.

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Bentea, Eduard Mihai ; Moore, Cynthia ; Deneyer, Lauren ; Verbruggen, Lise ; Churchill, Madeline J ; Hood, Rebecca L ; Meshul, Charles K ; Massie, Ann. / Plastic changes at corticostriatal synapses predict improved motor function in a partial lesion model of Parkinson's disease. In: Brain Research Bulletin. 2017 ; Vol. 130. pp. 257-267.

BibTeX

@article{78d4d29343e2454fbe7845e3ecdfcf79,
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.",
keywords = "Acetylcysteine/administration & dosage, Animals, Behavior, Animal, Cerebral Cortex/drug effects, Corpus Striatum/drug effects, Disease Models, Animal, Male, Mice, Inbred C57BL, Motor Activity/drug effects, Neural Pathways/drug effects, Neuronal Plasticity/drug effects, Parkinson Disease/pathology, Parkinsonian Disorders/chemically induced, Pars Compacta/drug effects, Post-Synaptic Density/drug effects, Rotarod Performance Test, Synapses/drug effects",
author = "Bentea, {Eduard Mihai} and Cynthia Moore and Lauren Deneyer and Lise Verbruggen and Churchill, {Madeline J} and Hood, {Rebecca L} and Meshul, {Charles K} and Ann Massie",
note = "Copyright {\circledC} 2017 Elsevier Inc. All rights reserved.",
year = "2017",
month = "4",
doi = "10.1016/j.brainresbull.2017.02.005",
language = "English",
volume = "130",
pages = "257--267",
journal = "Brain Research Bulletin",
issn = "0361-9230",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Plastic changes at corticostriatal synapses predict improved motor function in a partial lesion model of Parkinson's disease

AU - Bentea, Eduard Mihai

AU - Moore, Cynthia

AU - Deneyer, Lauren

AU - Verbruggen, Lise

AU - Churchill, Madeline J

AU - Hood, Rebecca L

AU - Meshul, Charles K

AU - Massie, Ann

N1 - Copyright © 2017 Elsevier Inc. All rights reserved.

PY - 2017/4

Y1 - 2017/4

N2 - 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.

AB - 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.

KW - Acetylcysteine/administration & dosage

KW - Animals

KW - Behavior, Animal

KW - Cerebral Cortex/drug effects

KW - Corpus Striatum/drug effects

KW - Disease Models, Animal

KW - Male

KW - Mice, Inbred C57BL

KW - Motor Activity/drug effects

KW - Neural Pathways/drug effects

KW - Neuronal Plasticity/drug effects

KW - Parkinson Disease/pathology

KW - Parkinsonian Disorders/chemically induced

KW - Pars Compacta/drug effects

KW - Post-Synaptic Density/drug effects

KW - Rotarod Performance Test

KW - Synapses/drug effects

UR - http://www.scopus.com/inward/record.url?scp=85014483336&partnerID=8YFLogxK

U2 - 10.1016/j.brainresbull.2017.02.005

DO - 10.1016/j.brainresbull.2017.02.005

M3 - Article

C2 - 28232022

VL - 130

SP - 257

EP - 267

JO - Brain Research Bulletin

JF - Brain Research Bulletin

SN - 0361-9230

ER -

ID: 30247827