Stimulation-induced depletion of vesicles, fatigue of transmission and recovery processes at a vertebrate central synapse.

The Mauthner fiber giant fiber synapses of the hatchetfish are chemically transmitting axo-axionic synapses in the medulla. Tetanic stimulation at room temperature depletes the presynaptic Mauthner terminal of vesicles and leads to the appearance of large numbers of irregular membraneous compartments in the terminal. Stimulation during cooling to 12 degrees C depletes the terminal of vesicles and greatly increases the external surface, which forms large whorls of invaginating double membranes. Many coated vesicles are attached to the surface and the invaginating whorls. It is concluded that vesicles are discharged by exocytosis and fusion of their membrane with the external surface, and that at room temperature, membrane is reinternalized by coated vesicles and formed into irregular compartments. In completion of the cycle, these compartments disappear, and the vesicle population recovers over an hour or two of rest. When the Mauthner fibers are stimulated at low rates, the p.s.p.'s in the giant fibers are large and suprathreshold. Minature p.s.p.'s are generated spontaneously or can be evoked by subthreshold depolarization or tetanic stimulation of the Mauthner fiber. Stimulation of the Mauthner fibers at gradually increasing frequencies depresses p.s.p. amplitude to or below the level of miniature p.s.p.'s, but no failures are observed. Small p.s.p.'s without failures suggest that the quantum number remains high but that quantal size is greatly reduced, either by partial filling, as is supported by the morphological observation of vesicle depletion, or by desensitization. When stimulation is stopped, recovery of p.s.p. amplitude occurs in 1 or 2 seconds, but if tetanic stimulation is resumed immediately, p.s.p. amplitude decreases again and much more rapidly than in the initial rundown. This result suggests that depression of p.s.p. amplitude is not due to desensitization and leaves partial filling as the most likely explanation of small quanta. Calculated quantal size following a tetanus recovers in 200-500 ms, which probably largely reflects the time for filling since enough vesicles can be supplied to prevent failures with much shorter intervals between stimuli. Because quantal size appears to decrease gradually as stimulation frequency increases, it appears that release of vesicles can interrupt filling, leading to the conclusion that filling and release sites are very close together. This conlusion is consistent with other data in the literature obtained by different techniques.