Correlation of non-uniform protein expression with variation in transmitter release probability

Abstract

The strength of synaptic transmission is highly variable between different synapses. The present study examined some factors that may contribute to this variation in the strength of neurotransmission in sympathetic varicosities of the mouse vas deferens. Transmitter release was measured using a focal macropatch electrode placed over pairs of visualised varicosities. By regulating the calcium concentration of the solutions inside the recording electrode and in the bath independently of each other, transmitter release was restricted to one or two surface varicosities at each recording site. Using this technique, transmitter release probability was shown to be highly variable, even between adjacent varicosities on single axon branches. Very little variation was observed in the calcium influx following single impulse nerve stimulation between adjacent Oregon Green BAPTA-1 loaded varicosities. However, the staining intensities of three vesicular proteins, SV2, synaptophysin, and synaptotagmin 1, showed considerable variation between adjacent varicosities on single axon branches. This variation in staining intensity may be partly explained by variation in the density of synaptic vesicles. However, double staining experiments using two vesicular antigens showed some varicosities staining for one vesicular antigen, but not for the second, suggesting that the expression of these release machinery proteins is regulated locally within the varicosities. The results of the present study strengthen suggestions that synaptic strength is at least in part, regulated by variation in the expression of vesicular proteins.

Seasonal regulation of quantal neurotransmitter release from amphibian neuromuscular junctions

“…, unpublished observations from the Lavidis laboratory has ascertained that N-type VGCCs are wholly responsible for the evoked neurotransmitter release since ω-connotoxin GVIA totally abolished evoked neurotransmitter release.During the dry season, evoked neurotransmitter release decreases as toads hibernate(Bennett & Lavidis 1991a, Hudson et al 2005, Knight et al 2005, Lavidis et al 2008. The results from the present study show that evoked neurotransmission is more susceptible to dynorphin-A inhibition during the dry season.…”

“…Unlike other organs which undergo a significant reduction in tissue mass after prolonged inactivity, reduction in metabolism is not accompanied by significant change in amphibian skeletal muscle mass. Dormant amphibian NMJs also maintain normal morphology when compared with the nondormant controls but exhibit a significant drop in the strength of synaptic neurotransmission(Bennett & Lavidis 1991a, Hudson et al 2005, Knight et al 2005, Lavidis et al 2008. How neuroendocrine systems coordinate decreases in muscle metabolic rate and yet maintain muscle mass and NMJ structure even after years of dormancy remains unclear.…”

Methods of measuring activity at individual synapses: A review of techniques and the findings they have made possible

“…The amplitude histogram of these single-synapse waveforms was well-fit by a single Gaussian (Table 4). This group also used the technique to compare function and expression of release-related proteins at sympathetic varicosities (Knight et al, 2005).…”