Abstract

The connection strength of most chemical synapses changes dynamically during normal use as a function of the recent history of activity. The phenomenon is known as short-term synaptic plasticity or synaptic dynamics, and is thought to be involved in processing and filtering information as it is transmitted across the synaptic cleft. Multiple presynaptic mechanisms have been implicated, but large gaps remain in our understanding of how the mechanisms are modulated and how they interact. One important factor is the timing of recruitment of synaptic vesicles to a readily-releasable pool. A number of studies have concluded that activity and/or residual Ca2+ can accelerate the mechanism, but alternative explanations for some of the evidence have emerged. Here I review the methodology that we have developed for isolating the recruitment and the dependence on activity from other kinds of mechanisms that are activated concurrently.

Highlights

  • Presynaptic terminals typically contain hundreds of vesicles laden with neurotransmitter, but, at any given time, only a few per cent are docked at the plasma membrane and are ready to undergo exocytosis on demand

  • These results suggest that the autapse preparation is a good model for synapses in ex vivo tissue, and by extension, in vivo, at least for studying rate-limiting mechanisms involved in synaptic vesicle recruitment to the readily releasable pool (RRP)

  • Multiple concerns have been raised that could complicate the interpretation of some experiments designed to measure activity and residual Ca2+-dependent acceleration of the mechanism by which vesicles are recruited to the RRP

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Summary

INTRODUCTION

Presynaptic terminals typically contain hundreds of vesicles laden with neurotransmitter, but, at any given time, only a few per cent are docked at the plasma membrane and are ready to undergo exocytosis on demand. These readily releasable vesicles are often described as constituents of a readily releasable pool (RRP). The results do not rule out serial models where slow-releasing vesicles can be recruited to the fast-releasing subdivision in addition to undergoing exocytosis directly, but we believe that our conclusions are valid whether or not transfer between subdivisions can occur (Mahfooz et al, 2016)

THE CAVEATS
Enhanced Fusogenicity
Fast Replenishment of EGTA-Sensitive Subdivisions
DETECTING ACCELERATION WITH OSMOTIC SHOCKS
RELEVANCE OF AUTAPTIC SYNAPSES TO NATIVE SYNAPSES IN TISSUE
CONTROLS FOR CONFIRMING RRP EXHAUSTION DURING TRAINS OF ACTION POTENTIALS
RESOLVING LIMITS WITH TRAINS OF ACTION POTENTIALS
CAVEATS RELATED TO ESTIMATING RRP CAPACITY
10. PARADIGM LEVEL CONCERNS
11. MOLECULAR EFFECTORS
Findings
12. SUMMARY
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