The role of the cerebellum in thalamic development

Brain development is susceptible to genetic or environmental perturbations that can disrupt normal maturation and produce life-long deficits.

This has primarily been studied in sensory systems, where manipulations of the external environment (for example sensory deprivation) profoundly impact the maturation of the thalamo-cortical system.

However, we lack understanding of the development of higher-order regions, such as the prefrontal cortex (PFC), whose function is linked to cognition rather than sensory perception.

This knowledge is important given many neurodevelopmental disorders display cognitive symptoms associated with PFC dysfunction. To date, it has been unclear what would be analogous to sensory deprivation for cognitive brain regions.

The cerebellum plays a role in cognition and provides excitatory drive to thalamo-cortical circuits targeting the PFC and other frontal cortices, in many ways mirroring ascending sensory innervation.

Based on this evidence, my hypothesis is that the cerebellum fulfils a similar role to the external environment in sensory cortices, relaying a cognitive and motor map to frontal cortices via parallel outputs to thalamus.

This proposal will use powerful genetic tools in mice to determine the topography of cerebellar outputs and test the cerebellum’s role in the maturation of thalamic regions that project to the PFC.

This question is important to our understanding of cognitive development and relevant to neurodevelopmental disorders, including schizophrenia and autism, whose pathophysiology includes dysfunction within these brain networks.

These findings will therefore provide key insight into the potential for miswiring in neurodevelopmental disorders and help guide therapeutic interventions to improve the lives of patients.