Fig. 11. Developmental changes in the endocytic properties of the growth cone. Top: at early stages of differentiation (3 DIV), constitutive high-capacity plasma-membrane recycling occurs via a bulk endocytic pathway mediated by large compartments (red) in the T domain of the growth cone. SV precursors (white circles), which, at these stages, are not prone to either constitutive or evoked recycling, do not participate in the bulk retrieval process. Middle: as neuronal differentiation proceeds (4-5 DIV), the intensity of the bulk recycling process decreases (orange) concomitantly with the emergence of activity-dependent SV recycling (green circles) in both the growth cone and nascent synaptic structures. Bottom: bulk plasma-membrane retrieval ceases at later stages of neuronal differentiation (7 DIV), when frequent interactions of the growth cone with targets result in the establishment of synaptic contacts associated with robust activity-dependent SV recycling. Exo-endocytosis of SVs is maintained also in the growth cone. The dissociation of bulk endocytosis from the SV recycling pathway at the onset of synaptogenesis might preserve the molecular identity of the forming pool of SVs and the stability of nascent synaptic structures.