Calcium dependence of neurotransmitter release at a high fidelity synapse.
TLDR
In this article, the authors investigated the Ca2+-sensitivity of vesicle priming, fusion, and replenishment at mossy fiber synapses in the rodent cerebellum.Abstract:
The Ca2+-dependence of the priming, fusion, and replenishment of synaptic vesicles are fundamental parameters controlling neurotransmitter release and synaptic plasticity. Despite intense efforts, these important steps in the synaptic vesicles' cycle remain poorly understood due to the technical challenge in disentangling vesicle priming, fusion, and replenishment. Here, we investigated the Ca2+-sensitivity of these steps at mossy fiber synapses in the rodent cerebellum, which are characterized by fast vesicle replenishment mediating high-frequency signaling. We found that the basal free Ca2+ concentration (<200 nM) critically controls action potential-evoked release, indicating a high-affinity Ca2+ sensor for vesicle priming. Ca2+ uncaging experiments revealed a surprisingly shallow and non-saturating relationship between release rate and intracellular Ca2+ concentration up to 50 μM. The rate of vesicle replenishment during sustained elevated intracellular Ca2+ concentration exhibited little Ca2+-dependence. Finally, quantitative mechanistic release schemes with five Ca2+ binding steps incorporating rapid vesicle replenishment via parallel or sequential vesicle pools could explain our data. We thus show that co-existing high- and low-affinity Ca2+ sensors mediate priming, fusion, and replenishment of synaptic vesicles at a high-fidelity synapse.read more
Citations
More filters
Journal ArticleDOI
Transient docking of synaptic vesicles: Implications and mechanisms
TL;DR: Transient docking as discussed by the authors shows that synaptic vesicles can rapidly and reversibly transit between docking and undocking during activity, which can account for many aspects of synaptic physiology, including physiological processes at the synapse that it may support.
Journal ArticleDOI
Different priming states of synaptic vesicles underlie distinct release probabilities at hippocampal excitatory synapses
TL;DR: In this paper , the authors show that CA1 pyramidal cells to fast spiking interneuron (FSIN) connections have 10-fold larger release probability (Pv) than those on oriens lacunosum-moleculare (O-LM) interneurons.
Journal ArticleDOI
Neurotransmitters, neuropeptides and calcium in oocyte maturation and early development
TL;DR: This review aims to provide an overview of the reported neurotransmitters and neuropeptides that participate in early stages of development and their association with Ca2+ signaling.
Journal ArticleDOI
Upregulated Ca2+ Release from the Endoplasmic Reticulum Leads to Impaired Presynaptic Function in Familial Alzheimer’s Disease
TL;DR: The model reveals that during prolonged stimulation, pathological Ca2+ signaling increases depression and desynchronization with stimulus, causing affected synapses to operate unreliably, providing direct evidence in support of a crucial role played by altered Ca2-homeostasis mediated by intracellular stores in FAD.
Posted ContentDOI
Upregulated Ca2+ release from the endoplasmic reticulum leads to impaired presynaptic function in Alzheimer’s disease
TL;DR: The model reveals that during prolonged stimulation, pathological Ca2+ signalling increases depression and desynchronization with stimulus, causing affected synapses to operate unreliably, providing direct evidence in support of a crucial role played by altered Ca 2+ homeostasis mediated by intracellular stores in AD.
References
More filters
Journal ArticleDOI
Short-Term Synaptic Plasticity
Robert S. Zucker,Wade G. Regehr +1 more
TL;DR: The evidence for this hypothesis, and the origins of the different kinetic phases of synaptic enhancement, as well as the interpretation of statistical changes in transmitter release and roles played by other factors such as alterations in presynaptic Ca(2+) influx or postsynaptic levels of [Ca(2+)]i are discussed.
Journal ArticleDOI
The synaptic vesicle cycle
TL;DR: Insight into how Munc18-1 collaborates with SNARE proteins in fusion, how the vesicular Ca2+ sensor synaptotagmin 1 triggers fast release, and how thevesicular Rab3 protein regulates release by binding to the active zone proteins RIM1 alpha and RIM2 alpha has advanced the understanding of neurotransmitter release.
Journal ArticleDOI
The role of calcium in neuromuscular facilitation
Bernard Katz,Ricardo Miledi +1 more
TL;DR: The hypothesis is put forward that a residue of the ‘active calcium’ which enters the terminal axon membrane during the nerve impulse is responsible for short‐term facilitation.
Journal ArticleDOI
Vesicle pools and Ca2+ microdomains: new tools for understanding their roles in neurotransmitter release.
TL;DR: The results obtained allowed us to assess the importance of knowing the carrier and removal status of canine coronavirus, as a source of infection for other animals, not necessarily belonging to the same breeds.
Journal ArticleDOI
Neurotransmitter Release: The Last Millisecond in the Life of a Synaptic Vesicle
TL;DR: This work has shown that direct flow of Ca(2+) ions from Ca( 2+) channels to synaptotagmin, which then triggers fusion, thus mediating tight millisecond coupling of an action potential to neurotransmitter release.