scholarly journals A Three-Pool Model Dissecting Readily Releasable Pool Replenishment at the Calyx of Held

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Jun Guo ◽  
Jian-long Ge ◽  
Mei Hao ◽  
Zhi-cheng Sun ◽  
Xin-sheng Wu ◽  
...  

Abstract Although vesicle replenishment is critical in maintaining exo-endocytosis recycling, the underlying mechanisms are not well understood. Previous studies have shown that both rapid and slow endocytosis recycle into a very large recycling pool instead of within the readily releasable pool (RRP) and the time course of RRP replenishment is slowed down by more intense stimulation. This finding contradicts the calcium/calmodulin-dependence of RRP replenishment. Here we address this issue and report a three-pool model for RRP replenishment at a central synapse. Both rapid and slow endocytosis provide vesicles to a large reserve pool (RP) ~42.3 times the RRP size. When moving from the RP to the RRP, vesicles entered an intermediate pool (IP) ~2.7 times the RRP size with slow RP-IP kinetics and fast IP-RRP kinetics, which was responsible for the well-established slow and rapid components of RRP replenishment. Depletion of the IP caused the slower RRP replenishment observed after intense stimulation. These results establish, for the first time, a realistic cycling model with all parameters measured, revealing the contribution of each cycling step in synaptic transmission. The results call for modification of the current view of the vesicle recycling steps and their roles.

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Jun Guo ◽  
Jian-long Ge ◽  
Mei Hao ◽  
Zhi-cheng Sun ◽  
Xin-sheng Wu ◽  
...  

1985 ◽  
Vol 108 (4) ◽  
pp. 511-517 ◽  
Author(s):  
Nandalal Bagchi ◽  
Birdie Shivers ◽  
Thomas R. Brown

Abstract. Iodine in excess is known to acutely inhibit thyroidal secretion. In the present study we have characterized the time course of the iodine effect in vitro and investigated the underlying mechanisms. Labelled thyroid glands were cultured in vitro in medium containing mononitrotyrosine, an inhibitor of iodotyrosine deiodinase. The rate of hydrolysis of labelled thyroglobulin was measured as the proportion of labelled iodotyrosines and iodothyronines recovered at the end of culture and was used as an index of thyroidal secretion. Thyrotrophin (TSH) administered in vivo acutely stimulated the rate of thyroglobulin hydrolysis. Addition of Nal to the culture medium acutely inhibited both basal and TSH-stimulated thyroglobulin hydrolysis. The effect of iodide was demonstrable after 2 h, maximal after 6 h and was not reversible upon removal of iodide. Iodide abolished the dibutyryl cAMP induced stimulation of thyroglobulin hydrolysis. Iodide required organic binding of iodine for its effect but new protein or RNA synthesis was not necessary. The inhibitory effects of iodide and lysosomotrophic agents such as NH4C1 and chloroquin on thyroglobulin hydrolysis were additive suggesting different sites of action. Iodide added in vitro altered the distribution of label in prelabelled thyroglobulin in a way that suggested increased coupling in the thyroglobulin molecule. These data indicate that 1) the iodide effect occurs progressively over a 6 h period, 2) continued presence of iodide is not necessary once the inhibition is established, 3) iodide exerts its action primarily at a post cAMP, prelysosomal site and 4) the effect requires organic binding of iodine, but not new RNA or protein synthesis. Our data are consistent with the hypothesis that excess iodide acutely inhibits thyroglobulin hydrolysis by increasing the resistance of thyroglobulin to proteolytic degradation through increased iodination and coupling.


1976 ◽  
Vol 68 (2) ◽  
pp. 225-NP ◽  
Author(s):  
J. F. MORRIS

SUMMARY The distribution of neurosecretory granules in various anatomical compartments of neurosecretory axons of the neural lobe of the rat pituitary has been studied. Apart from the most anterior tip of the gland, where granules are largely restricted to undilated axons and a few 'swellings', the proportional compartmental storage of granules is essentially homogeneous for the rest of the gland: 13% of granules are found in undilated axons, 31% in axonal 'endings' (which contain microvesicles and abut the basement membrane) and 55% in axonal 'swellings' (which are devoid of significant numbers of microvesicles). These values indicate that the 'endings' contain a much greater proportion of the total number of granules stored in the neural lobe than would be predicted if the readily releasable pool of hormone were composed of all the granules in the 'endings'. Some further constraint on granule release either physiological or anatomical (e.g. the position of the granule in relation to the plasmalemma of the 'ending') must be operative.


1979 ◽  
Vol 83 (1) ◽  
pp. 53-59 ◽  
Author(s):  
A. J.-M. C. PICKERING ◽  
G. FINK

SUMMARY The size of the 'readily releasable pool' of luteinizing hormone at various times of the oestrous cycle has been determined by injecting a supramaximal dose of luteinizing hormone releasing factor (LH-RF) i.v. into rats anaesthetized with sodium pentobarbitone. In an attempt to block replenishment of the 'pool' during release, cycloheximide was administered 30 min before LH-RF. A 20-fold increase in pool size occurred between the morning of dioestrus and the evening of pro-oestrus in the absence of any significant change in total pituitary content of LH. This suggests that increased responsiveness may be brought about by a change in the receptor-release apparatus and/or a transfer of LH from a 'storage pool' which leads to an apparent increase in the proportion of LH available for release.


PLoS Biology ◽  
2015 ◽  
Vol 13 (10) ◽  
pp. e1002267 ◽  
Author(s):  
Taulant Bacaj ◽  
Dick Wu ◽  
Jacqueline Burré ◽  
Robert C. Malenka ◽  
Xinran Liu ◽  
...  

2007 ◽  
Vol 97 (1) ◽  
pp. 948-950 ◽  
Author(s):  
Jane M. Sullivan

Paired-pulse depression (PPD) is a form of short-term plasticity that plays a central role in processing of synaptic activity and is manifest as a decrease in the size of the response to the second of two closely timed stimuli. Despite mounting evidence to the contrary, PPD is still commonly thought to reflect depletion of the pool of synaptic vesicles available for release in response to the second stimulus. Here it is shown that PPD cannot be accounted for by depletion at excitatory synapses made by hippocampal neurons because PPD is unaffected by changes in the fraction of the readily releasable pool (RRP) released by the first of a pair of pulses.


2019 ◽  
Author(s):  
Yun Zhu ◽  
Dainan Li ◽  
Hai Huang

ABSTRACTRetrieval of synaptic vesicles via endocytosis is essential for maintaining sustained synaptic transmission, especially for neurons that fire action potentials at high frequencies. However, how activity regulates synaptic vesicles recycling is largely unknown. Here we report that Na+ substantially accumulated in the mouse calyx of Held terminals during repetitive high-frequency spiking. Elevated presynaptic Na+ accelerated both slow and rapid forms of endocytosis and facilitated endocytosis overshoot but did not affect the readily releasable pool size, Ca2+ influx, or exocytosis. To examine whether this facilitation of endocytosis is related to the Na+-dependent vesicular content change, we dialyzed increasing concentrations of glutamate into the presynaptic cytosol or blocked the vesicular glutamate uptake with bafilomycin and found the rate of endocytosis was not affected by regulating the glutamate content in the presynaptic terminal. Endocytosis is critically dependent on intracellular Ca2+, and the activity of Na+/Ca2+ exchanger (NCX) may be altered when the Na+ gradient is changed. However, neither NCX blocker nor change of extracellular Na+ concentration affected the endocytosis rate. Moreover, two-photon Ca2+ imaging showed that presynaptic Na+ did not affect the action potential-evoked intracellular Ca2+ transient and decay. Therefore, we revealed a novel mechanism of cytosolic Na+ in accelerating vesicle endocytosis. During high-frequency synaptic transmission, when large amounts of synaptic vesicles are fused, Na+ accumulated in terminals, facilitated vesicle recycling and sustained reliable synaptic transmission.


2020 ◽  
Vol 287 (1931) ◽  
pp. 20201079 ◽  
Author(s):  
Clara Hozer ◽  
Fabien Pifferi

The biological clock expresses circadian rhythms, whose endogenous period (tau) is close to 24 h. Daily resetting of the circadian clock to the 24 h natural photoperiod might induce marginal costs that would accumulate over time and forward affect fitness. It was proposed as the circadian resonance theory. For the first time, we aimed to evaluate these physiological and cognitive costs that would partially explain the mechanisms of the circadian resonance hypothesis. We evaluated the potential costs of imposing a 26 h photoperiodic regimen compared to the classical 24 h entrainment measuring several physiological and cognitive parameters (body temperature, energetic expenditure, oxidative stress, cognitive performances) in males of a non-human primate ( Microcebus murinus ), a nocturnal species whose endogenous period is about 23.5 h. We found significant higher resting body temperature and energy expenditure and lower cognitive performances when the photoperiodic cycle length was 26 h. Together these results suggest that a great deviation of external cycles from tau leads to daily greater energetic expenditure, and lower cognitive capacities. To our knowledge, this study is the first to highlight potential mechanisms of circadian resonance theory.


Sign in / Sign up

Export Citation Format

Share Document