Figure 9.

Summary schematic illustrating the three distinct phases of regenerative PF wiring in wild-type mice (top) and the arrested regeneration in GluD2-KO mice (bottom). Three dendritic domains are colored in blue for PCD-I, cyan for PCD-II, and green for PCD-III. In wild-type mice, PF axons and synapses massively degenerate after PF transection. In this degenerative phase, numerous free spines emerge and the PF territory expands aberrantly. Then, PF synapses enlarge, and there is an increase in the contact ratio with PC spines (to 1:2) in the hypertrophic phase. In this phase, the number and density of PF synapses nearly recover to normal levels, and free spines nearly completely disappear, but PF density remains low. In the remodeling phase, PF density increases, at least partly through sprouting and elongation of PF collaterals, and PF synapses reacquire a compact structure and a 1:1 contact ratio with PC spines. This suggests that competitive synaptic wiring by PFs and CFs onto PCs is regained in wild-type mice. In contrast, in the GluD2-KO mice, the degenerative phase persists, without a shift to the hypertrophic or remodeling phases of PF–PC regenerative rewiring.