Diversification of synaptic strength: presynaptic elements

Key Points Synapses are functionally diverse. For example, synaptic strength can differ markedly from one synapse to the next. How does this diversity arise? What are its underlying mechanisms? Both structural and molecular explanations have been put forward to account for synaptic differentiation. It is possible to define two general cases of synaptic functional differentiation. In case I, different branches of the same neuron evoke synaptic responses of diverse character in various follower cells. It is thought that retrograde influences from the follower cells determine synaptic properties. In case II, different presynaptic neurons that supply the same follower cell evoke different postsynaptic responses. In this case, upstream determination of presynaptic properties seems to be more significant. From a presynaptic perspective, how could synaptic structure modify synaptic strength? There are several possibilities. Specifically, there might be presynaptic differences in the number of active zones per synapse, the density of Ca 2+ channels in the active zone, the size of synaptic vesicles, the spacing between vesicles and Ca 2+ channels, and the number of readily releasable vesicles. There is evidence for the contribution of each of these factors to synaptic differentiation of both invertebrate and vertebrate synapses. Although quantal size has been thought to depend largely on postsynaptic factors, several presynaptic factors might also affect this variable. They include variations in the size of vesicles, in the intravesicular transmitter concentration or in the properties of the fusion event. However, the contribution of differences in quantal size to synaptic diversity under normal circumstances is not fully understood. The size of the readily releasable vesicle pool also contributes to differences in synaptic strength. There is a linear relationship between docked and readily releasable vesicles, and the readily releasable pool size is tightly linked to release probability and to synapse size. These relationships have been best established for synapses in culture; although they have been postulated to apply also to synapses in vivo , their validity remains to be tested. The number of synaptic Ca 2+ channels and the type of channel might also affect synaptic strength. However, evidence for such a link is, at best, suggestive, as crucial physiological experiments that show a causal relationship in situ are still lacking. Differences in vesicle–channel