Cerebellar control of Cortical Development

Project Information

CERCODE

Grant agreement ID: 950013

DOI

10.3030/950013

EC signature date 27 November 2020

Start date 1 January 2021

End date 31 December 2026

Funded under

• EXCELLENT SCIENCE - European Research Council (ERC)

Total cost

€ 1 499 709,26

EU contribution

€ 1 499 709,26

Coordinated by

AGENCIA ESTATAL CONSEJO SUPERIOR DE INVESTIGACIONES CIENTIFICAS
Spain

Periodic Reporting for period 3 - CERCODE (Cerebellar control of Cortical Development)

Reporting period: 2024-01-01 to 2025-06-30

Summary of the context and overall objectives of the project

Clinical studies have produced compelling evidence indicating that early cerebellar damage is a significant risk factor for the emergence of autism spectrum disorders. Moreover, these cerebellar lesions lead to a broad spectrum of changes in both structure and function of the developing cerebral cortex, suggesting that these alterations may underlie the cerebellar origin of these complex disorders.
Despite the importance of these findings, the specific mechanisms through which the cerebellum influences the development and maturation of distant cortical circuits remain largely elusive. To address this critical knowledge gap, the overall objective of the CERCODE project is to investigate the consequences of early cerebellar disruptions on remote cortical circuits.
To achieve these objectives, we are developing models with cerebellar alterations to study their anatomical and functional impacts and understand how the cortex reacts to cerebellar disruption during development.
In this research, we aim to uncover invaluable insights into the role of atypical cerebellar structure or function in the development of the cerebral cortex, paving the way for advances in our understanding of the pathogenesis of neurodevelopmental disorders of cerebellar origin.

Work performed from the beginning of the project to the end of the period covered by the report and main results achieved so far

In the first part of the project, we are studying how the cerebellum establishes connections with intermediate targets, such as the thalamus, that link it to the cortex. These results suggest that connectivity develops from the late embryonic to the early postnatal stages.
After defining these temporospatial windows, in which the cerebellum can communicate with the cortex, we successfully developed models of early cerebellar disruptions. By combining various techniques, we are analyzing, from diverse perspectives, the impact of these alterations on the development of these distal regions.
Our analysis suggests a potential role for the developing cerebellum in influencing the development of these regions.

Progress beyond the state of the art and expected potential impact (including the socio-economic impact and the wider societal implications of the project so far)

One of the major obstacles to the development of better treatments is the lack of understanding of the complex cellular and molecular mechanisms underlying cerebellar diseases. Thus, fundamental research focusing on how cerebellar circuits develop and how the brain adapts after a cerebellar lesion is indispensable for the development of new therapeutic approaches.
However, an explanation of how developmental alterations of the cerebellum are derived in some high-order neurodevelopmental disorders (i.e. autism) is missing. Our results provide a first step toward understanding the mechanisms that shape the development and maturity of distant networks after cerebellar alterations. They will also provide the necessary background for follow-up on the study of cerebellar implications in neurodevelopmental disorders.