Estimating the Readily-Releasable Vesicle Pool Size at Synaptic Connections in the Neocortex
Estimating the Readily-Releasable Vesicle Pool Size at Synaptic Connections in the Neocortex
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DOI：
10.3389/fnsyn.2019.00029
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发表时间：
2019-10-15
影响因子：
3.7
通讯作者：
Ramaswamy, Srikanth
中科院分区：
文献类型：
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作者：
Barros-Zulaica, Natali;Rahmon, John;Ramaswamy, Srikanth
以往的研究基于突触传递的“量子模型”，表明神经递质的释放是由新皮层中单个突触接触处的单个释放位点介导的。然而，最近的研究似乎与这一假设相矛盾，并表明多囊泡释放（MVR）可以更好地解释在体外观察到的突触反应的变异性。在这项研究中，我们提出了一种新的方法来估计每个突触的释放位点的数量，也被称为容易释放池（N-RRP）的大小，从配对的第5层厚簇状锥体细胞（L5_TTPC）在幼年大鼠体感皮层之间的连接的全细胞记录。我们的方法扩展了Loebel等人的工作。（2009）利用最近发表的数据驱动的新皮层组织的生物物理模型。使用这种方法，我们估计L5_TTPC之间突触连接的N-RRP在2到3之间。为了约束N-RRP值的其他连接的微电路，我们开发和验证了一种泛化方法，使用已发表的数据的变异系数（CV）的突触后电位（PSP）的幅度从文献中，并比较它们对在硅片实验。我们的研究预测，在新皮层突触连接的递质释放可以介导的MVR，并提供了一个数据驱动的方法来约束微电路中的MVR模型参数。
Previous studies based on the 'Quantal Model' for synaptic transmission suggest that neurotransmitter release is mediated by a single release site at individual synaptic contacts in the neocortex. However, recent studies seem to contradict this hypothesis and indicate that multi-vesicular release (MVR) could better explain the synaptic response variability observed in vitro. In this study we present a novel method to estimate the number of release sites per synapse, also known as the size of the readily releasable pool (N-RRP), from paired whole-cell recordings of connections between layer 5 thick tufted pyramidal cell (L5_TTPC) in the juvenile rat somatosensory cortex. Our approach extends the work of Loebel et al. (2009) by leveraging a recently published data-driven biophysical model of neocortical tissue. Using this approach, we estimated N-RRP to be between two to three for synaptic connections between L5_TTPCs. To constrain N-RRP values for other connections in the microcircuit, we developed and validated a generalization approach using published data on the coefficient of variation (CV) of the amplitudes of post-synaptic potentials (PSPs) from literature and comparing them against in silico experiments. Our study predicts that transmitter release at synaptic connections in the neocortex could be mediated by MVR and provides a data-driven approach to constrain the MVR model parameters in the microcircuit.