REMODELING OF FUNCTIONAL CONNECTIVITY AT GRANULE CELL–PURKINJE CELL SYNAPSES IN THE MOUSE CEREBELLUM

The cerebellum is involved in motor coordination and is divided into anatomo-functional modules processing sensorimotor information from specific body part. This information is conveyed by mossy fibers to granule cells (GC) contacting Purkinje cells (PC) of different modules via their long axons, the parallel fibers (PFs). PFs underlie inter-modular communication, which may be at the core of motor coordination. Therefore, the main goal of our research is to understand how intermodular communication in the cerebellar cortex underlies motor adaptation.
Using patterned light photostimulation combined with patch-clamp recordings in acute cerebellar slices, we showed that PC are connected to clusters of GCs of different modules, while most remain silent, thus forming a specific connectivity map (CoMap). CoMaps are conserved across mice in lobules III, IV and V of the cerebellar cortex, but they reorganize when the locomotor context changes. We set out to elucidate the molecular mechanisms underlying CoMap reorganization. Using electrical stimulation paired with patch-clamp recordings in acute slices, we identified a high-frequency stimulation protocol, known to induce LTP at GC-PC synapses, that awakens 50% of previously silent synapses. Moreover, blocking mGluR1 receptors or using Cav3.1 knockout mice, both essential for LTP, also completely blocks the awakening of these synapses.
These findings demonstrate that mGluR1- and Cav3.1-dependent plasticity recruits previously silent GC–PC synapses, dynamically reshaping CoMap between cerebellar modules and thereby modulating intermodular information processing for motor adaptation.