Subcellular presynaptic membrane

There is evidence tliat PrP " in neurons is concenttated in die synaptic region. The protein is axonally transported to nerve terminals (Borchelt et al, 1994) and is enriched in presynaptic membranes obtained by subcellular fractionation (Herms et al, 1999). It has also been localized to synaptic profiles by immunoelectron microscopy (Fournier et al, 1995 Sales et al, 1998). By light microscopic immuno-cytochemistry, PrP " is found primarily in synaptic fields of the olfactory bulb, limbic structures, striatonigral complex, and cerebellar molecular layer, with little staining of neuronal perikarya or fiber pathways (Sales etal, 1998 Herms etal, 1999). These data would suggest a role for PrP in synaptic function, although additional studies are clearly necessary. 

When an action potential traveling down the axon of a motoneuron reaches the myoneural endplate, a process occurs that releases acetylcholine into the synaptic cleft and consequently depolarizes the postsynaptic membrane. A similar process probably occurs at cholinergic synapses in the central nervous system. In 1950 Fatt and Katz discovered a spontaneous subthreshold activity (MEPP) of motor nerve endings and were thereby led to the concept that acetylcholine is released in definite units (quanta) of 10 to 10 molecules. Electron microscopy subsequently revealed characteristic vesicles about 40 nm in diameter, clustered near presynaptic membranes. Subcellular fractionation procedures were devised by Whittaker and de Robertis for the isolation of these vesicles from brain homogenates in sucrose density gradients, and it was soon demonstrated that they were indeed concentrated reservoirs of acetylcholine. The hypothesis that the vesicles discharge the quanta of transmitter became irresistible. 

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