Cellular and molecular mechanisms of synapse elimination in the Mammalian brain

: Neurons form exuberant synapses with target cells early in development. Then, necessary synapses are strengthened whereas unnecessary connections are weakened and eventually eliminated during postnatal development. This process, known as synapse elimination, is widely believed to be a crucial step for shaping immature neural circuits into functionally mature versions. In the neonatal mouse cerebellum, each Purkinje cell is innervated by multiple climbing fibers (CFs). Their synaptic strengths are initially uniform but a single CF strengthens relative to the other CFs during the first postnatal week. Then the weaker CFs are eliminated during the second postnatal week. Similar developmental changes occur in several other synapses including the neuromuscular junction and the projection from the retina to the lateral geniculate nucleus (LGN). Recent studies have clarified that synapse elimination consists of multiple phases that involve distinct types of neural activity and/or molecular mechanisms.