Cellular determinants of network dynamics and plasticity in the cerebellar cortex. (360G-Wellcome-064452_Z_01_A)

Understanding the representation and storage of information in the mammalian brain requires knowledge of how single neurons contribute to generating patterns of network activity and how these patterns are modified by experience. In this proposal I will link cellular mechanisms of synaptic integration and plasticity to the functional behaviour of neuronal networks in the intact rodent cerebellar cortex. Experiments will focus on dendritic signalling in the three major inhibitory cell types in cerebellar cortex: Purkinje neurons, molecular layer interneurons, and Golgi cells. This will be addressed first in slice preparations using a combination of dendritic patch-clamp recordings and imaging of calcium and voltage-sensitive dye signals. These experiments will be linked to the network level by making targeted patch-clamp recordings from labelled neurons in vivo to study their input-output relationships during integration of different types of sensory input (auditory, visual and somatosensory). The spatiotemporal dynamics of activity in identified populations of neurons will be examined via optical imaging in conjunction with 2-photon imaging of calcium signals in single neurons and populations of neurons. Finally, I will use these tools to identify the locus of plasticity in the neural circuits of the cerebellum triggered by behaviourally relevant patterns of activity.