Modelling vesicular release at hippocampal synapses.
Modelling vesicular release at hippocampal synapses.
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DOI：
10.1371/journal.pcbi.1000983
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发表时间：
2010-11-11
影响因子：
4.3
通讯作者：
Levine H
中科院分区：
文献类型：
--
作者：
Nadkarni S;Bartol TM;Sejnowski TJ;Levine H
我们在一个随机的、空间显式的CA3-CA1突触前突触的生物物理模型中研究了导致囊泡融合的局部钙动力学。囊泡释放的动力学模型有两个钙传感器，一个持续几十毫秒的快速同步释放传感器和一个持续几百毫秒的缓慢异步释放的单独传感器。只有在包括发布之间持续几毫秒的不稳定时期时，才能一致地解释范围广泛的数据。包含第二个用于异步释放的传感器，具有缓慢的解结合部位，从而具有长记忆，通过促进释放影响短期可塑性。我们的模拟还揭示了囊泡释放的第三个时间尺度，该时间尺度与刺激相关，不同于快速释放和缓慢释放。在这些详细的蒙特卡罗模拟中，囊泡释放的三个时间尺度都对突触超微结构的空间细节不敏感。此外，我们的模拟使我们能够识别突触传递的普遍特征和那些受结构调制的特征。当从突触前神经元的神经末梢释放的神经递质向突触后神经元发出事件发生的信号时，神经元中的化学突触传递就会发生。我们研究的目标是模拟在海马体中发现的一种突触的释放，海马体是大脑中与学习和记忆有关的一部分。突触模型是在计算机中模拟的，该计算机跟踪神经末梢中的所有重要分子。该模型导致了对现有实验数据的更好理解，包括导致单个神经递质包释放的确切条件。根据我们的模型，多个包的释放可以由单个突触前事件触发，但包是一次释放一个包。此外，我们还揭示了一种以前没有研究过的极快释放形式背后的机制。该模型对突触的其他特性进行了预测，这些特性可以在实验中进行测试。更好地了解海马体中正常的突触是如何工作的，将有助于我们更好地了解抑郁症和精神分裂症等精神障碍中突触的问题。
We study local calcium dynamics leading to a vesicle fusion in a stochastic, and spatially explicit, biophysical model of the CA3-CA1 presynaptic bouton. The kinetic model for vesicle release has two calcium sensors, a sensor for fast synchronous release that lasts a few tens of milliseconds and a separate sensor for slow asynchronous release that lasts a few hundred milliseconds. A wide range of data can be accounted for consistently only when a refractory period lasting a few milliseconds between releases is included. The inclusion of a second sensor for asynchronous release with a slow unbinding site, and thereby a long memory, affects short-term plasticity by facilitating release. Our simulations also reveal a third time scale of vesicle release that is correlated with the stimulus and is distinct from the fast and the slow releases. In these detailed Monte Carlo simulations all three time scales of vesicle release are insensitive to the spatial details of the synaptic ultrastructure. Furthermore, our simulations allow us to identify features of synaptic transmission that are universal and those that are modulated by structure. Chemical synaptic transmission in neurons takes place when a neurotransmitter released from a nerve terminal of the presynaptic neuron signals to the postsynaptic neuron that an event has occurred. The goal of our research was to model the release at a type of synapse found in the hippocampus, a part of the brain that is involved with learning and memory. The synapse model was simulated in a computer that kept track of all of the important molecules in the nerve terminal. The model led to a better understanding of the extant experimental data including exact conditions that lead to the release of a single packet of neurotransmitter. According to our model, the release of more than one packet can be triggered by a single presynaptic event but the packets are released one at a time. Furthermore, we uncovered the mechanisms underlying an extremely fast form of release that had not been previously studied. The model made predictions for other properties of the synapse that can be tested experimentally. A better understanding of how the normal synapses in the hippocampus work will help us to better understand what goes wrong with synapses in mental disorders such as depression and schizophrenia.
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影响因子：
25
作者：
Fredj, Naila Ben;Burrone, Juan
通讯作者：
Burrone, Juan
单个海马GABA能突触的突触后反应的释放概率依赖性尺度。
DOI：
10.1523/jneurosci.3106-06.2006
发表时间：
2006-11-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Biró AA;Holderith NB;Nusser Z
通讯作者：
Nusser Z
影响因子：
64.8
作者：
GULYAS, AI;MILES, R;FREUND, TF
通讯作者：
FREUND, TF
影响因子：
25
作者：
Fusi, Stefano;Abbott, L. F.
通讯作者：
Abbott, L. F.
影响因子：
--
作者：
Carmignoto, G;Fellin, T
通讯作者：
Fellin, T