Synaptic vesicle relationships with the presynaptic membrane as shown by a new method of fast chemical fixation

Brief vascular perfusion of the rat brain with a mixture of concentrated aldehydes completely insolubilized the brain protein in less than 30 s and yielded excellent ultrastructural preservation. Abundant synaptic vesicles closely and specifically attached to the presynaptic membrane were constantly detected. These vesicles appeared to undergo progressive transformation into amorphous, electron-dense material. No evidence of vesicle exocytosis was detected in the brains perfused in vivo but fixations performed 1 h after death showed abundant exocytotic-like images. The results suggest that the vesicles may not be exocytotically released to the intersynaptic cleft but disintegrate intracytoplasmically in the immediate vicinity of the presynaptic membrane.