神经肌肉递质释放位点结构和功能的微生理建模。

IF 2.8 4区 医学 Q2 NEUROSCIENCES
Frontiers in Synaptic Neuroscience Pub Date : 2022-06-13 eCollection Date: 2022-01-01 DOI:10.3389/fnsyn.2022.917285
Rozita Laghaei, Stephen D Meriney
{"title":"神经肌肉递质释放位点结构和功能的微生理建模。","authors":"Rozita Laghaei,&nbsp;Stephen D Meriney","doi":"10.3389/fnsyn.2022.917285","DOIUrl":null,"url":null,"abstract":"<p><p>The general mechanism of calcium-triggered chemical transmitter release from neuronal synapses has been intensely studied, is well-known, and highly conserved between species and synapses across the nervous system. However, the structural and functional details within each transmitter release site (or active zone) are difficult to study in living tissue using current experimental approaches owing to the small spatial compartment within the synapse where exocytosis occurs with a very rapid time course. Therefore, computer simulations offer the opportunity to explore these microphysiological environments of the synapse at nanometer spatial scales and on a sub-microsecond timescale. Because biological reactions and physiological processes at synapses occur under conditions where stochastic behavior is dominant, simulation approaches must be driven by such stochastic processes. MCell provides a powerful simulation approach that employs particle-based stochastic simulation tools to study presynaptic processes in realistic and complex (3D) geometries using optimized Monte Carlo algorithms to track finite numbers of molecules as they diffuse and interact in a complex cellular space with other molecules in solution and on surfaces (representing membranes, channels and binding sites). In this review we discuss MCell-based spatially realistic models of the mammalian and frog neuromuscular active zones that were developed to study presynaptic mechanisms that control transmitter release. In particular, these models focus on the role of presynaptic voltage-gated calcium channels, calcium sensors that control the probability of synaptic vesicle fusion, and the effects of action potential waveform shape on presynaptic calcium entry. With the development of these models, they can now be used in the future to predict disease-induced changes to the active zone, and the effects of candidate therapeutic approaches.</p>","PeriodicalId":12650,"journal":{"name":"Frontiers in Synaptic Neuroscience","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236679/pdf/","citationCount":"1","resultStr":"{\"title\":\"Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites.\",\"authors\":\"Rozita Laghaei,&nbsp;Stephen D Meriney\",\"doi\":\"10.3389/fnsyn.2022.917285\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The general mechanism of calcium-triggered chemical transmitter release from neuronal synapses has been intensely studied, is well-known, and highly conserved between species and synapses across the nervous system. However, the structural and functional details within each transmitter release site (or active zone) are difficult to study in living tissue using current experimental approaches owing to the small spatial compartment within the synapse where exocytosis occurs with a very rapid time course. Therefore, computer simulations offer the opportunity to explore these microphysiological environments of the synapse at nanometer spatial scales and on a sub-microsecond timescale. Because biological reactions and physiological processes at synapses occur under conditions where stochastic behavior is dominant, simulation approaches must be driven by such stochastic processes. MCell provides a powerful simulation approach that employs particle-based stochastic simulation tools to study presynaptic processes in realistic and complex (3D) geometries using optimized Monte Carlo algorithms to track finite numbers of molecules as they diffuse and interact in a complex cellular space with other molecules in solution and on surfaces (representing membranes, channels and binding sites). In this review we discuss MCell-based spatially realistic models of the mammalian and frog neuromuscular active zones that were developed to study presynaptic mechanisms that control transmitter release. In particular, these models focus on the role of presynaptic voltage-gated calcium channels, calcium sensors that control the probability of synaptic vesicle fusion, and the effects of action potential waveform shape on presynaptic calcium entry. With the development of these models, they can now be used in the future to predict disease-induced changes to the active zone, and the effects of candidate therapeutic approaches.</p>\",\"PeriodicalId\":12650,\"journal\":{\"name\":\"Frontiers in Synaptic Neuroscience\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2022-06-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9236679/pdf/\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Frontiers in Synaptic Neuroscience\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3389/fnsyn.2022.917285\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2022/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"NEUROSCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Synaptic Neuroscience","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3389/fnsyn.2022.917285","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"NEUROSCIENCES","Score":null,"Total":0}
引用次数: 1

摘要

钙触发的神经突触化学递质释放的一般机制已经被深入研究,是众所周知的,并且在整个神经系统的物种和突触之间高度保守。然而,每个递质释放位点(或活性区)的结构和功能细节很难用现有的实验方法在活组织中研究,因为突触内的空间很小,胞吐发生的时间过程非常快。因此,计算机模拟提供了在纳米空间尺度和亚微秒时间尺度上探索突触这些微生理环境的机会。由于突触的生物反应和生理过程发生在随机行为占主导地位的条件下,模拟方法必须由这种随机过程驱动。MCell提供了一种强大的模拟方法,它采用基于粒子的随机模拟工具来研究现实和复杂(3D)几何中的突触前过程,使用优化的蒙特卡罗算法来跟踪有限数量的分子,因为它们在复杂的细胞空间中与溶液和表面(代表膜,通道和结合位点)中的其他分子扩散和相互作用。在这篇综述中,我们讨论了基于mccell的哺乳动物和青蛙神经肌肉活动区的空间逼真模型,这些模型被开发用于研究控制递质释放的突触前机制。这些模型特别关注突触前电压门控钙通道的作用,控制突触囊泡融合概率的钙传感器,以及动作电位波形形状对突触前钙进入的影响。随着这些模型的发展,它们现在可以在未来用于预测疾病引起的活性区变化,以及候选治疗方法的效果。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites.

Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites.

Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites.

Microphysiological Modeling of the Structure and Function of Neuromuscular Transmitter Release Sites.

The general mechanism of calcium-triggered chemical transmitter release from neuronal synapses has been intensely studied, is well-known, and highly conserved between species and synapses across the nervous system. However, the structural and functional details within each transmitter release site (or active zone) are difficult to study in living tissue using current experimental approaches owing to the small spatial compartment within the synapse where exocytosis occurs with a very rapid time course. Therefore, computer simulations offer the opportunity to explore these microphysiological environments of the synapse at nanometer spatial scales and on a sub-microsecond timescale. Because biological reactions and physiological processes at synapses occur under conditions where stochastic behavior is dominant, simulation approaches must be driven by such stochastic processes. MCell provides a powerful simulation approach that employs particle-based stochastic simulation tools to study presynaptic processes in realistic and complex (3D) geometries using optimized Monte Carlo algorithms to track finite numbers of molecules as they diffuse and interact in a complex cellular space with other molecules in solution and on surfaces (representing membranes, channels and binding sites). In this review we discuss MCell-based spatially realistic models of the mammalian and frog neuromuscular active zones that were developed to study presynaptic mechanisms that control transmitter release. In particular, these models focus on the role of presynaptic voltage-gated calcium channels, calcium sensors that control the probability of synaptic vesicle fusion, and the effects of action potential waveform shape on presynaptic calcium entry. With the development of these models, they can now be used in the future to predict disease-induced changes to the active zone, and the effects of candidate therapeutic approaches.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
CiteScore
7.10
自引率
2.70%
发文量
74
审稿时长
14 weeks
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信