During the implementation of the grant, the overall scientific goals were achieved in the project.
First, we have described how the cerebellar axons contact with the thalamus during early brain development. To this aim we used a novel approach that combined in utero viral injections to trace the axons, clearing methods and 3D light sheet microscopy (WP1). Our results allowed us to study in three-dimensions how the cerebellar axons innervate the thalamus during development. These results point out that already at early stages of development cerebellar axons have the potential to influence immature motor and non-motor thalamic circuits.
Next aim was to clarify whether the cerebellum could influence the development of the thalamus. Thus, in the following step, we developed a strategy to manipulate the cerebello-thalamic connectivity (WP2) and study the impact on the development of the thalamus (WP3-WP4).
We reported that abnormal cerebellar inputs to the thalamus could alter the thalamocortical circuits. Furthermore, we observed that it triggers the alteration in the expression of genes involved in critical processes for brain development and wiring.
In summary, work performed under the present project adds to our understanding the temporal and spatial window by which the cerebellum could start to influence the development and maturation of thalamocortical circuits. Furthermore, we started to elucidate the molecular mechanism involved in those alterations, which it is a critical step forward towards the understanding of the cerebellar implication in high-order neurodevelopmental disorders.
The findings from the project have been disseminated among the scientific community in international conferences and among the general public in outreach activities.
