scholarly journals Deficit in Motor Skill Consolidation-Dependent Synaptic Plasticity at Motor Cortex to Dorsolateral Striatum Synapses in a Mouse Model of Huntington’s Disease

eNeuro ◽  
2020 ◽  
Vol 7 (2) ◽  
pp. ENEURO.0297-19.2020
Author(s):  
Christelle Glangetas ◽  
Pedro Espinosa ◽  
Camilla Bellone
2019 ◽  
Author(s):  
Christelle Glangetas ◽  
Pedro Espinosa ◽  
Camilla Bellone

Huntington's disease (HD) is a neurodegenerative disease notably characterized by progressive motor symptoms. Although the loss of Medium Spiny Neurons (MSNs) in the striatum has been associated with motor deficits, premanifest patients already present cognitive deficiencies and show early signs of motor disabilities. Here in a YAC128 HD mouse model, we identified impairment in motor skill learning at the age of 11 to 14 weeks. Using optogenetic stimulation, we found that excitatory synaptic transmission from motor cortex to MSNs located in the Dorso Lateral part of the Striatum (DLS) is altered. Using single pellet reaching task, we observed that while motor skill learning is accompanied by a dynamic change in AMPA/NMDA ratio in wild type mice, this form of synaptic plasticity does not occur in YAC128 mice. This study not only proposes new meaningful insight the synaptopathic mechanisms of HD, but also highlights that deficit in motor skill learning dependent synaptic plasticity at motor cortex to DLS synapses represents an early biomarker for Huntington's disease.


2021 ◽  
Author(s):  
Sophie C. Andrews ◽  
Dylan Curtin ◽  
James P. Coxon ◽  
Julie C. Stout

Abstract Huntington’s disease (HD) mouse models suggest that cardiovascular exercise may enhance neuroplasticity and delay disease signs, however, the effects of exercise on neuroplasticity in people with HD are unknown. Using a repeated-measures experimental design, we compared the effects of a single bout of high-intensity exercise, moderate-intensity exercise, or rest, on motor cortex synaptic plasticity in 14 HD CAG-expanded participants (9 premanifest & 5 early manifest) and 20 CAG-healthy control participants, using transcranial magnetic stimulation. Measures of cortico-motor excitability, short-interval intracortical inhibition and intracortical facilitation were obtained before and after a 20-minute bout of either high-intensity interval exercise, moderate-intensity continuous exercise, or rest, and again after intermittent theta burst stimulation (iTBS). HD participants showed less inhibition at baseline compared to controls. Whereas the control group showed increased excitability and facilitation following high-intensity exercise and iTBS, the HD group showed no differences in neuroplasticity responses following either exercise intensity or rest, with follow-up Bayesian analyses providing consistent evidence that these effects were absent in the HD group. These findings indicate that exercise-induced synaptic plasticity mechanisms in response to acute exercise may be attenuated in HD, and demonstrate the need for future research to further investigate exercise and plasticity mechanisms in people with HD.


2018 ◽  
Vol 147 (2) ◽  
pp. 222-239 ◽  
Author(s):  
Juliana G. Doria ◽  
Jessica M. de Souza ◽  
Flavia R. Silva ◽  
Isabella G. Olmo ◽  
Toniana G. Carvalho ◽  
...  

2018 ◽  
Vol 24 (4) ◽  
pp. 353-363 ◽  
Author(s):  
Victor G. Gómez-Pineda ◽  
Francisco M. Torres-Cruz ◽  
César I. Vivar-Cortés ◽  
Elizabeth Hernández-Echeagaray

2020 ◽  
Author(s):  
Sara Fernández-García ◽  
Sara Conde-Berriozabal ◽  
Esther García-García ◽  
Clara Gort-Paniello ◽  
David Bernal-Casas ◽  
...  

AbstractHuntington’s disease (HD) is a neurological disorder characterized by motor disturbances. HD pathology is most prominent in the striatum, the central hub of basal ganglia. The cortex is the main striatal afference and progressive cortico-striatal disconnection characterizes HD. We mapped cortico-striatal dysfunction in HD mice to ultimately modulate the activity of selected cortico-striatal circuits to ameliorate motor symptoms and recover synaptic plasticity. Multimodal MRI in vivo suggested prominent functional network deficits in fronto-striatal compared to motor-striatal pathways, which were accompanied by reduced glutamate levels in the striatum of HD mice. Moreover, optogenetically-stimulated glutamate release from fronto-striatal terminals was reduced in HD mice and electrophysiological responses in striatal neurons were blunted. Remarkably, repeated M2 Cortex-dorsolateral striatum optogenetic stimulation normalized motor behavior in HD mice and evoked a sustained increase of synaptic plasticity. Overall, these results reveal that the selective stimulation of fronto-striatal pathways can become an effective therapeutic strategy in HD.


2017 ◽  
Vol 38 (3) ◽  
pp. 544-554 ◽  
Author(s):  
Marja D. Sepers ◽  
Amy Smith-Dijak ◽  
Jeff LeDue ◽  
Karolina Kolodziejczyk ◽  
Ken Mackie ◽  
...  

2006 ◽  
Vol 15 (10) ◽  
pp. 1690-1703 ◽  
Author(s):  
Austen J. Milnerwood ◽  
Damian M. Cummings ◽  
Glenn M. Dallérac ◽  
Jacki Y. Brown ◽  
Sarat C. Vatsavayai ◽  
...  

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