Interrogating cerebellar contributions to cortical computations during goal-directed behaviour

The nervous system's essential functions rely on complex, distributed neural activity. While the forebrain and cerebellum were once thought to operate independently, they share overlapping functions, raising key questions: How are their subcircuit connections specified? Do brain regions process information locally or collectively? Understanding these interactions is crucial for decoding brain-wide computations that drive behaviour.
The cerebellum is organized into modules, where climbing fiber input from the inferior olive and mossy fiber input from the forebrain converge onto Purkinje cell microzones, which in turn project to cerebellar nuclei (CbNs). CbNs form the cerebellum's output, linking back to the neocortex via the thalamus, creating long-range loops.
Traditionally, the cerebellum is thought to generate internal models that predict the sensory consequences of movement. However, whether this principle extends to broader cerebellar functions remains unclear. Advances in population imaging, multiregional recordings, and targeted perturbations in goal-directed tasks now enable precise investigation of cerebellar contributions to distributed brain computations.
To determine how cerebellar outputs influence motor control dynamics in the forebrain and behaviour, I will perform simultaneous two-photon calcium imaging and channelrhodopsin-based stimulation of Purkinje cells using holographic pattern generators to perturb the cerebellum with microzonal specificity. This approach, combined with Neuropixel electrophysiological recordings in the motor cortex, will allow me to map the transfer function between the cerebellum and motor forebrain and examine their shared dynamics during behaviour. Ultimately, I aim to develop a computational framework for cerebellar-cortical interactions, enabling intelligent perturbation-based models to modulate goal-directed behaviour through microzonal-specific interventions.