MOTOR LEARNING RESHAPES CEREBELLAR CORTEX CONNECTIVITY THROUGH GLIA-DEPENDENT SYNAPTIC PRUNING

Motor learning requires neural circuits to adapt their connectivity in response to experience. The cerebellum, with its highly ordered organization and essential role in motor coordination, provides an ideal framework to study how learning reshapes synaptic networks. While plasticity at Purkinje cell synapses has been widely studied, how motor learning alters Purkinje cell connectivity remains unclear.
Here, we combined a complex running wheel paradigm with monosynaptic rabies virus tracing to map presynaptic inputs onto Purkinje cells during motor skill acquisition. Motor learning induced a robust increase in several Purkinje cell inputs, particularly in young animals, with a progressive decline in this form of plasticity with ageing. Notably, despite the marked increase in the traced connectivity, electrophysiological assessment showed that the number and proportion of functional inputs to Purkinje cells remained unchanged, hinting to an accelerated synaptic turnover rather than expansion of the presynaptic connectome per se. To test this hypothesis we conditionally ablated the gene Atg5, a key component in the autophagic/phagocytic machinery, in cerebellar Bergmann glia, given their established role in Purkinje cell synaptic pruning. In Bergmann glia Atg5-deficient mice, exposure to motor learning led to an aberrant accumulation of presynaptic inputs onto Purkinje cells, which was functionally reflected by a delayed acquisition of complex motor skills.
Together, these findings demonstrate that motor learning reshapes cerebellar connectivity through tightly regulated synaptic turnover, which is mediated by Bergmann glia.