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Elucidating the Superior Colliculus-related network properties and modulation in Huntington's Disease mouse model to delay the onset and ameliorate severity of the motor symptoms

Objective

Neurodegenerative movement disorders e.g. Huntington’s Disease (HD) predominantly involve progressive motor symptoms as a result of disrupted basal ganglia neuronal networks. These symptoms are accompanied by early occurring deficits in visual perception and oculomotor functions, which share neuronal circuits with motor domains, and can be used in the prediction of the onset and severity of HD pathogenesis. Therefore, understanding the early circuitry alterations in HD progression is crucial to develop new disease-modifying strategies. The superior colliculus (SC) is a sensorimotor structure that receives and integrates visual information to control reflexes and is involved in visual perception and oculomotor functions. Functional MRI and behavioural studies demonstrated that the HD symptomatic mouse model show alterations in the SC function, but its role in motor symptoms has not been directly addressed.
The HD-SC project proposes that (i) SC is an important factor in the basal ganglia circuit alterations found in HD, (ii) topographically segregated SC outputs provide differential contributions to the motor and defensive behaviours, and (iii) temporal control of SC neuronal plasticity with novel phytochromes will cause delay and amelioration in motor symptoms in HD model. This will be addressed using a combination of mouse behavioural, histological and biochemical phenotyping to reveal the onset of SC-related alterations in the HD model. Then, by using DREADDS we will determine the differential representation of SC outputs in motor and defensive behaviour. Finally, we will test the capability of phytochromes to modulate SC neuronal plasticity and delay and ameliorate motor symptoms in the HD model. Overall, the HD-SC aims at bringing a spotlight to mechanisms causing symptomatic resilience in the HD model, which potentially could be implemented in other neurodegenerative movement disorders with basal ganglia circuit alterations.

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Topic(s)

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HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European Fellowships

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Call for proposal

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(opens in new window) HORIZON-MSCA-2022-PF-01

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Coordinator

UNIVERSITAT DE BARCELONA
Net EU contribution

Net EU financial contribution. The sum of money that the participant receives, deducted by the EU contribution to its linked third party. It considers the distribution of the EU financial contribution between direct beneficiaries of the project and other types of participants, like third-party participants.

€ 165 312,96
Address
GRAN VIA DE LES CORTS CATALANES 585
08007 BARCELONA
Spain

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Region
Este Cataluña Barcelona
Activity type
Higher or Secondary Education Establishments
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Total cost

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