Bone morphogenetic protein signaling in structural plasticity of cerebellar mossy fibers

Establishment of precise neural wiring is crucial for proper functioning of the brain. Neuronal circuits are formed and refined during embryonic and postnatal development. However, mature circuits and their connections remain plastic and can change with learning and adaptation. Structural plasticity is one fundamental way in which neuroplasticity is achieved, and it involves changes in morphology and number of synapses. While is it well-described that structural plasticity can be elicited by specific patterns of neuronal activity, the molecular and cellular mechanisms underlying such structural changes are poorly understood.
The cerebellum is a brain structure best known for its role in coordinating skilled, fine tuned movements and motor learning. The cerebellar circuit is an ideal model to study structural plasticity because its cellular elements are simple and well characterized. Mossy fibers, arising from a collection of precerebellar nuclei, relay cortical and proprioceptive information to Purkinje cells indirectly via granule cell. Purkinje cells integrate mossy fiber information with inputs directly received from climbing fiber afferents emerging from the inferior olivary nucleus. Golgi cells, an inhibitory interneuron that is innervated by mossy fibers, control timing and distribution of mossy fiber-derived information, resulting in feedforward inhibition. Structural growth of this feedforward inhibition was implicated in motor learning. However, the molecular mechanism of such structural plasticity and most forms of structural plasticity remains largely unknown.
Here, I report that the canonical Bone Morphogenetic Protein (BMP) pathway is a positive regulator of structural plasticity of cerebellar mossy fibers. I demonstrate that structural plasticity of cerebellar mossy fibers can be elicited by mossy fiber activation. Furthermore, I present data that suggests that BMP signaling pathway is regulated during learning. In sum, this work highlights novel roles for BMP signaling pathway in cerebellar circuit, extending beyond early developmental functions.