Integration and plasticity of sensory-evoked synaptic input in single cerebellar interneurones in vivo (360G-Wellcome-078222_Z_05_Z)

Inhibitory microcircuits play a key role in regulating excitability in neuronal networks throughout the brain. However, little is known about the extent to which interneurone circuits are modifiable by sensory experience and the mechanisms involved in such modifications. This project will investigate the plasticity of inhibitory connections in the molecular layer of the cerebellar cortex in vivo by combining two recently developed techniques - in vivo patch-clamp recording and 2-photon imaging - in order to identify the locus of plasticity driven by sensory input in these cerebellar inhibitory circuits. First, whole-cell patch-clamp recordings will be made from Purkinje cells in vivo in order to determine if patterns of sensory stimulation (e.g. whisker deflections) can trigger long-term modification of inhibitory synaptic input to these neurones. Second, we will fill interneurones and Purkinje cells with fluorescent calcium dyes and image dendritic calcium signals in vivo in order to determine if activity-dependent changes are triggered by particular patterns of dendritic calcium signaling. Finally, the experiments will be complemented by compartmental modeling of interneurones and Purkinje cells based on our experimental data. These combined approaches will provide important new insights into how interneurone networks encode changes in sensory experience.