Endocytosis at ribbon synapses.

Unlike conventional synaptic terminals that release neurotransmitter episodically in response to action potentials, neurons of the visual, auditory and vestibular systems encode sensory information in graded signals that are transmitted at their synapses by modulating the rate of continuous release. The synaptic ribbon, a specialized structure found at the active zones of these neurons, is necessary to sustain the high rates of exocytosis required for continuous release. To maintain the fidelity of synaptic transmission, exocytosis must be balanced by high-capacity endocytosis, to retrieve excess membrane inserted during vesicle fusion. Capacitance measurements following vesicle release in ribbon-type neurons indicate two kinetically distinct phases of compensatory endocytosis, whose relative contributions vary with stimulus intensity. The two phases can be independently regulated and may reflect different underlying mechanisms operating on separate pools of recycling vesicles. Electron microscopy shows diversity among ribbon-type synapses in the relative importance of clathrin-mediated endocytosis versus bulk membrane retrieval as mechanisms of compensatory endocytosis. Ribbon synapses, like conventional synapses, make use of multiple endocytosis pathways to replenish synaptic vesicle pools, depending on the physiological needs of the particular cell type.