Synapse‐to‐synapse variation in mean synaptic vesicle size and its relationship with synaptic morphology and function

Abstract

Synaptic vesicle (SV) size is one parameter that controls the amount of neurotransmitter released from individual SVs and, therefore, is fundamental to our understanding of synaptic function. The recently discovered variability of mean SV size among excitatory hippocampal synapses -- if actively regulated -- is a potential mechanism for the regulation of transmitter release. Here, we investigated which parameters influence mean SV size. First, we revealed that synapse-to-synapse variability of SV size is a general phenomenon in several species and brain regions. In addition, we determined the relationship between mean SV size and synaptic morphology. In three-dimensional reconstructions from serial ultrathin sections, we found that SV size did not correlate with the area of the postsynaptic density (a measure for synaptic size and synaptic cleft volume) nor with the total number of SVs within a bouton or bouton volume. We tested the long-held hypothesis that a change in osmotic pressure (potentially caused by a change in neurotransmitter concentration) affects SV size. When we reduced the osmotic pressure, SVs became significantly smaller; however, an increase in osmotic pressure had no effect on SV size. Furthermore, we found that SV size does not adapt to chronic changes in activity and that the SV cycle is capable of providing constant SV size during long-lasting, high-frequency stimulation.

Readily releasable vesicles recycle at the active zone of hippocampal synapses

“…To quantitatively address the size of labeled vesicles, we measured the area of typical electron lucent SVs and calculated the surface of these vesicles assuming they are spheres. As in previous reports (21,22), we found that SVs have an average diameter of 40 nm and a surface of 5,000 nm 2 . Next, we measured the area of labeled vesicles in synaptic profiles and found that labeled vesicle surfaces ranged from 5,000 to 20,000 nm 2 .…”

“…Because we could not detect a significant amount of coated vesicles that could support membrane retrieval after the release of the RRP, it seems likely that SV retrieval via coated pits and coated vesicles does not play a major role at hippocampal synapses at least not under our experimental conditions. On the other hand, there is overwhelming evidence that clathrin plays a central role in SV retrieval at hippocampal synapses (6,9,22). The lack of coated vesicles in our samples may suggest a function of clathrin in noncoated vesicle endocytosis.…”

Ultrastructure of Synapses in the Mammalian Brain

“…Presynaptic boutons of excitatory synapses contain round, clear vesicles ( 35 nm diameter) loaded with the neurotransmitter glutamate (Harris and Sultan 1995;Qu et al 2009). Vesicles distributed throughout the presynaptic bouton compose a "reserve" pool distinct from the anatomically docked vesicles that contact the presynaptic membrane at the AZ (Fig.…”

Small Liposomes Accelerate the Fibrillation of Amyloid β (1–40)

“…Moreover, the presence of A␤ peptides in the synapses in vivo caused a dysfunction in synaptic vesicles with a diameter of ϳ40 nm (36). Because the binding of A␤ peptides to a membrane and the subsequent deformation are a linked phenomenon, the presence of deformed membranes may accelerate the binding and fibrillation of A␤.…”