Activity-dependent axonal and synaptic plasticity in the cerebellum.

The cerebellum is a brain region endowed with a high degree of plasticity also in adulthood. After damage or alteration in the patterns of activity, it is able to undergo remarkable changes in its architecture and to form new connections based upon a process of synaptic reorganization. This review addresses cellular and molecular mechanisms that regulate the competition between two inputs belonging to different neuronal populations in innervating two contiguous but separate domains of the same target cell. The two inputs are the parallel fibers, the axon of the cerebellar granule cells, and the olivocerebellar neurons, that terminate as climbing fibers in the cerebellar cortex. The target is the Purkinje cell characterized by two dendritic domains that are different in size and number of spines, upon which the two afferent inputs impinge. Both inputs express several genes related to plasticity throughout the life span conferring the ability to remodel their synapses. In addition, we provided evidence that climbing fibers and Purkinje cells show remarkable reciprocal trophic interactions that are required for the maintenance of the correct synaptic connectivity. Through their activity, climbing fibers sustain the competition with parallel fibers by displacing this input to the distal territory of the Purkinje cell dendrite. In addition, they operate on the Purkinje cells through AMPA receptor suppressing spines in the territory surrounding their synapses. In this way, climbing fibers are able to optimize spine distribution and functional connectivity.