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Controlling forelimb actions through basal ganglia to brainstem signaling

Behavior arises through the combination of movements within distributed circuits. Most work in the past focused on high motor centers and executive circuits in the spinal cord, but how these systems are linked in order to function... ver más

01/12/2023

FMI

203K€

Presupuesto del proyecto: 203K€

Líder del proyecto

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL R... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Fecha límite participación Sin fecha límite de participación.

Financiación concedida El organismo H2020 notifico la concesión del proyecto el día 2023-12-01

MSCA-IF-2019: Individual Fellowships

I+D

Cerrada hace 5 años

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1 Participantes

FMI

203.15K€ | Lider

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Duración del proyecto: 44 meses Fecha Inicio: 2020-03-12
Fecha Fin: 2023-12-01

Líder del proyecto

FRIEDRICH MIESCHER INSTITUTE FOR BIOMEDICAL R... No se ha especificado una descripción o un objeto social para esta compañía.

TRL 4-5

Presupuesto del proyecto 203K€

Fecha límite de participación Sin fecha límite de participación.

Descripción del proyecto Behavior arises through the combination of movements within distributed circuits. Most work in the past focused on high motor centers and executive circuits in the spinal cord, but how these systems are linked in order to function is poorly understood. The substantia nigra reticulata (SNR), a basal ganglia output, sends projections to the brainstem. Yet how the brainstem processes these inputs to control actions remains unknown. The Arber lab discovered that the parvocellular reticular formation (PCRt) of the mouse brainstem harbors neurons controlling forelimb behaviors including reaching. PCRt neurons receive inhibitory inputs from the SNR. Thus, the SNR-PCRt circuit is an excellent stepping stone for understanding the mechanisms behind self-initiated actions. I propose to investigate the impact of the SNR signaling on the activity of PCRt neurons when a mouse self-initiates forelimb reaching. I will characterize the anatomy and nature of SNR to PCRt connections to understand whether and how this architecture supports forelimb movement. I will combine a behavioral task designed to isolate the neuronal events around the triggering of a self-initiated action with loss- and gain of function perturbations to unravel the building blocks of self-initiated actions. Finally, I will use the task while monitoring the activity of specific SNR and PCRt neurons to understand how the different actors physically implement the operations for self-initiated actions. Together, my experiments will disclose the fine-scale machinery for initiating and controlling an action. This level of understanding is key for designing new therapies to help people impaired in self- initiating actions such in Parkinson’s disease. The fellowship will provide me with the unique opportunity to expand my expertise and establish the foundations of my future career as an independent group leader.

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