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Delineating Convergent and Divergent Cortico-Cerebellar pathways in motor Control

Project description

Elucidating the structural and functional interconnectivity of the cortex and cerebellum

Scientists have made substantial progress in elucidating the structural and functional organisation of the cerebral cortex and cerebellum. While evidence suggests these regions are distinct yet interconnected computational entities, the functional significance of cortico-cerebellar interactions remains poorly understood. The ERC-funded CODI-MAP project investigates the hypothesis that extensive convergent and divergent cortico-cerebellar connectivity is critical for integrated function. The project will apply advanced methodologies, including combinatorial viral-genetic tracing, multi-regional electrophysiological and optical recording techniques, and computational modelling. This project aims to comprehensively reveal the detailed reciprocal anatomical and molecular architecture of cortico-cerebellar circuits, elucidate their dynamic interactions during goal-directed voluntary forelimb movements and clarify their role in sensorimotor learning.

Objective

The CODI-MAP aims to address a fundamental question: How do the cerebral cortex and cerebellum cooperate to generate and regulate movements? Despite their pivotal contribution to motor control, the complex nature of cortico-cerebellar interaction remains a mystery. Our recent work has demonstrated a significant interdependency between the cortical and cerebellar activities, however the precise architecture and computational strategy that cortico-cerebellar circuits employ to generate and maintain task specific information is unknown.
Here, I propose to comprehensively address the detailed reciprocal connectivity of the cortico-cerebellar circuits, their functional interaction during goal directed voluntary movements, as well as their contribution to sensorimotor learning. Our central hypothesis is that the cortico-cerebellar circuits form complex networks characterized by both extensive convergence and divergence. This configuration provides a spectrum of task-related functional modules for sensorimotor control and learning. By engaging specific functional modules, the cortico-cerebellar networks achieve the required spatiotemporal precision for directing movements. We will first systematically dissect the anatomical and molecular features of the cortico-cerebellar pathways using a suite of sophisticated combinatorial viral-genetic strategies. Next, we will identify and manipulate the functional circuits that control forelimb movements using novel multi-regional electrophysiological and optical methods. Finally, we will combine in silico simulation with dual-regional optical recording and manipulation to uncover the plastic changes within cortico-cerebellar circuits during learning.
The outcome of this project has the potential to challenge the conventional perspective that considers cortex and cerebellum as distinct computational entities, proposing a multi-regional integrative circuitry, thereby unveiling fundamental principles of how the brain generates action.

Keywords

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Programme(s)

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Topic(s)

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Funding Scheme

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HORIZON-ERC - HORIZON ERC Grants

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Call for proposal

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(opens in new window) ERC-2024-COG

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Host institution

ERASMUS UNIVERSITAIR MEDISCH CENTRUM ROTTERDAM
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.

€ 2 625 000,00
Address
DR MOLEWATERPLEIN 40
3015 GD Rotterdam
Netherlands

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Activity type
Higher or Secondary Education Establishments
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Total cost

The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.

€ 2 625 000,00

Beneficiaries (1)

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