Mapping sensory-motor cerebellar circuits for adaptive behaviour

The cerebellar cortex is thought to form predictive associations between sensory inputs and motor commands: animals leverage these associations to coordinate and adapt movements to contextual changes in the environment.

This sensory-motor control depends on Purkinje neurons, each of which receives sensory, motor and cognitive signals from one climbing fibre as well as thousands of parallel fibres, the axons of granule cells.

Despite years of anatomical work, cerebellar sensory-motor representations have not been mapped at the cellular scale; similarly, the functional circuit connectivity underlying sensory-motor integration remains unexplored.

To reveal the functional architecture of the mouse cerebellar cortex, I propose to use rabies monosynaptic tracing to map and functionally characterise the presynaptic ensemble of individual Purkinje neurons.

I will validate my functional connectomics strategy with electron microscopy and elucidate whether the anatomical organisation of presynaptic circuits converging on Purkinje neurons is modular or random (Aim1).

Then, I will harness functional imaging and optogenetics to map the topography of cortico-cerebellar representations, and discover whether Purkinje neurons pool inputs from related sensory-motor presynaptic modules (Aim2).

Finally I will train mice in a sensory-guided forelimb task, and ascertain how these circuits are engaged by sensory-motor events, and their timing, during adaptive behaviour (Aim3).