The First 100 nm Inside the Pre-synaptic Terminal Where Calcium Diffusion Triggers Vesicular Release

Guerrier, Claire; Holcman, David

doi:10.3389/fnsyn.2018.00023

Cited by 24 publications

(27 citation statements)

References 58 publications

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“…The results demonstrated the existence of constitutive differences in the PF terminals of lobules V and X of CB 1 ‐WT mice. These distinct features might reflect different synaptic vesicle trafficking dynamics and release probabilities that could have functional consequences on synaptic plasticity (Guerrier & Holcman, ; Singer & Diamond, ). In primary granule cell cultures, PF terminals have relatively large releasable vesicle pool, rapid vesicle replenishment, loose coupling of Ca 2+ channels and releasable vesicles as well as strong dependence of facilitation on fast intracellular Ca 2+ buffering (Kawaguchi & Sakaba, ).…”

Section: Discussionmentioning

confidence: 99%

“…Differences observed in CB 1 ‐KO relative to CB 1 ‐WT could be particularly relevant as the synaptic vesicle distribution in CB 1 ‐KO could affect the exposure of synaptic vesicles to the calcium sources that dictate vesicle dynamics (Böhme, Grasskamp, & Walter, ; Guerrier & Holcman, ) that are crucial for synaptic plasticity (Atwood, Lovinger, & Mathur, ; Böhme et al, ; Chen, Das, Nakamura, DiGregorio, & Young, ; Eggermann, Bucurenciu, Goswami, & Jonas, ; Guerrier & Holcman, ; Holderith et al, ; Indriati et al, ; Keller et al, ; Sheng et al, ). The structural basis of synaptic plasticity is mediated by the dynamics of the presynaptic architecture (Bruckner, Zhan, & O'Connor‐Giles, ).…”

Section: Discussionmentioning

confidence: 99%

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Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Buceta

Elezgarai

Rico‐Barrio

et al. 2019

J of Comparative Neurology

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The cannabinoid CB 1 receptor localizes to the glutamatergic parallel fiber (PF) terminals of the cerebellar granule cells and participates in synaptic plasticity, motor control and learning that are impaired in CB 1 receptor knockout (CB 1 -KO) mice. However, whether ultrastructural changes at the PF-Purkinje cell (PC) synapses occur in CB 1 -KO remains unknown. We studied this in the vermis of the spinocerebellar lobule V and the vestibulocerebellar lobule X of CB 1 -KO and wild-type (CB 1 -WT) mice by electron microscopy. Lobule V, but not lobule X, of CB 1 -KO had significantly less and longer synapses than in CB 1 -WT. PF terminals were significantly larger in both lobules of CB 1 -KO with no changes in PC dendritic spines. The PF terminals in lobule V of CB 1 -KO contained less synaptic vesicles and lower vesicle density; by contrast, vesicle density in lobule X of CB 1 -KO remained unchangeable relative to CB 1 -WT. There were as many vesicles in lobule V of CB 1 -KO as in CB 1 -WT, but their distribution decreased drastically at 300 nm of the active zone. In lobule X of CB 1 -KO, less vesicles were found within 150 nm from the presynaptic membrane; however, no vesicles were at 450-600 nm of the active zone. A significant higher amount of synaptic vesicles close to the active zone in lobule V and X of CB 1 -KO was observed. In conclusion, the absence of CB 1 receptors strikingly and distinctively impacts on the ultrastructural architecture of the PF-PC synapses located in cerebellar lobules that differ in vulnerability to damage and motor functions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Buceta

Elezgarai

Rico‐Barrio

et al. 2019

J of Comparative Neurology

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“…The vast majority of FPT studies have focused on the time it takes a given single searcher to find a target. However, several recent works and commentaries have shown that the relevant timescale in many systems is actually the time it takes the fastest searcher(s) to find a target out of a large group of searchers [11,12,13,14,15,16,17,18,19,20]. For example, roughly N = 10 8 sperm cells search for an egg in human reproduction, but fertilization occurs as soon as a single sperm cell finds the egg [21,22,23,24].…”

Section: Introductionmentioning

confidence: 99%

Distribution of extreme first passage times of diffusion

Lawley

2020

J. Math. Biol.

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Many events in biology are triggered when a diffusing searcher finds a target, which is called a first passage time (FPT). The overwhelming majority of FPT studies have analyzed the time it takes a single searcher to find a target. However, the more relevant timescale in many biological systems is the time it takes the fastest searcher(s) out of many searchers to find a target, which is called an extreme FPT. In this paper, we apply extreme value theory to find a tractable approximation for the full probability distribution of extreme FPTs of diffusion. This approximation can be easily applied in many diverse scenarios, as it depends on only a few properties of the short time behavior of the survival probability of a single FPT. We find this distribution by proving that a careful rescaling of extreme FPTs converges in distribution as the number of searchers grows. This limiting distribution is a type of Gumbel distribution and involves the LambertW function. This analysis yields new explicit formulas for approximations of statistics of extreme FPTs (mean, variance, moments, etc.) which are highly accurate and are accompanied by rigorous error estimates.

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“…Several exciting investigations and commentaries have recently announced a paradigm shift in studying cellular activation rates [1,2,3,4,5,6,7,8,9,10,11,12,13]. This important work has produced new questions, calls for more investigation, and intriguing conjectures to explain the seeming "redundancy" that marks many biological systems [2].…”

Section: Introductionmentioning

confidence: 99%

A Probabilistic Approach to Extreme Statistics of Brownian Escape Times in Dimensions 1, 2, and 3

Lawley¹,

Madrid²

2020

J Nonlinear Sci

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First passage time (FPT) theory is often used to estimate timescales in cellular and molecular biology. While the overwhelming majority of studies have focused on the time it takes a given single Brownian searcher to reach a target, cellular processes are instead often triggered by the arrival of the first molecule out of many molecules. In these scenarios, the more relevant timescale is the FPT of the first Brownian searcher to reach a target from a large group of independent and identical Brownian searchers. Though the searchers are identically distributed, one searcher will reach the target before the others and will thus have the fastest FPT. This fastest FPT depends on extremely rare events and its mean can be orders of magnitude faster than the mean FPT of a given single searcher. In this paper, we use rigorous probabilistic methods to study this fastest FPT. We determine the asymptotic behavior of all the moments of this fastest FPT in the limit of many searchers in a general class of two and three dimensional domains. Our results correct and extend recent results on this problem.

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The First 100 nm Inside the Pre-synaptic Terminal Where Calcium Diffusion Triggers Vesicular Release

Cited by 24 publications

References 58 publications

Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Distribution of extreme first passage times of diffusion

A Probabilistic Approach to Extreme Statistics of Brownian Escape Times in Dimensions 1, 2, and 3

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The First 100 nm Inside the Pre-synaptic Terminal Where Calcium Diffusion Triggers Vesicular Release

Cited by 24 publications

References 58 publications

Deletion of the cannabinoid CB1 receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Deletion of the cannabinoid CB1 receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Distribution of extreme first passage times of diffusion

A Probabilistic Approach to Extreme Statistics of Brownian Escape Times in Dimensions 1, 2, and 3

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Product

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Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses

Deletion of the cannabinoid CB₁ receptor impacts on the ultrastructure of the cerebellar parallel fiber‐Purkinje cell synapses