A model of graded synaptic transmission for use in dynamic network simulations.

A model of graded synaptic transmission for use in dynamic network simulations.
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用于动态网络模拟的分级突触传递模型。

DOI:
10.1152/jn.1993.69.4.1225
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发表时间:
1993
影响因子:
2.5
通讯作者:
Calabrese,RL
Calabrese,RL
中科院分区:
医学3区
文献类型:
--
作者:
DeSchutter,E;Angstadt,JD;Calabrese,RL

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1. 药用水蛭的心跳中枢模式产生网络包含基本的神经振荡器,包括相互抑制的节段性心脏中间神经元对,它们使用分级和尖峰介导的突触传递。我们正在开发这个图形发生器的通用计算机模型。我们的建模目标是探索促进心脏中间神经元振荡的膜电流和突触传递的相互作用。作为实现这一目标的第一步,我们已经开发了一个相互抑制性心脏中间神经元之间的梯度突触传递的计算机模型。先前收集的突触前Ca2+电流和同时的突触后电流和电位(5 mM外[Ca2+])的电压钳数据被用作模型的基础。2. 我们假设突触前Ca2+电流由不同的快(ICaF)和慢(Icas)组件组成,因为该电流有两个不同的失活时间过程。我们使用一阶活化和失活动力学对这些组分拟合标准霍奇金-赫胥黎方程(Eq. 1和2,附录)。3. 模型中的梯度突触传递是基于一个无量纲变量的计算[P]。由因子A决定的IcaF和ICaS的一部分都有助于[P],而去除因子B则降低[P](公式4,附录)。[P]可以大致等同于[Ca2+]在一个未指定的体积内,有效地引起递质释放。递质释放和突触后传导与[P]3有关(Eq. 3, APPENDIX)。4. 我们调整了我们的模型来收集生理外部[Ca2+] (2.0 mM)的电压钳数据,并对其进行了较短的突触前电压步骤测试。在所有条件下,突触前Ca2+电流和突触转移都得到了很好的模拟。5. 梯度突触传递模型可用于网络模拟,以再现一对相互抑制的心脏中间神经元的振荡活动。由于该模型中的突触传递是突触前Ca2+电流的明确功能,因此该模型应该有助于探索膜电流和突触传递之间的相互作用,从而促进和调节相互抑制性心脏中间神经元的振荡。
1. The heartbeat central pattern-generating network of the medicinal leech contains elemental neural oscillators, comprising reciprocally inhibitory pairs of segmental heart interneurons, that use graded as well as spike-mediated synaptic transmission. We are in the process of developing a general computer model of this pattern generator. Our modeling goal is to explore the interaction of membrane currents and synaptic transmission that promote oscillation in heart interneurons. As a first step toward this goal, we have developed a computer model of graded synaptic transmission between reciprocally inhibitory heart interneurons. Previously gathered voltage-clamp data of presynaptic Ca2+ currents and simultaneous postsynaptic currents and potentials (5 mM external [Ca2+]) were used as the bases of the model. 2. We assumed that presynaptic Ca2+ current was composed of distinct fast (ICaF) and slow (Icas) components because there are two distinct time courses of inactivation for this current. We fitted standard Hodgkin-Huxley equations (Eq. 1 and 2, APPENDIX) to these components using first-order activation and inactivation kinetics. 3. Graded synaptic transfer in the model is based on calculation of a dimensionless variable [P]. A portion of both IcaF and ICaS determined by a factor A contributes to [P], and a removal factor B decreases [P] (Eq. 4, APPENDIX). [P] can be roughly equated to the [Ca2+] in an unspecified volume that is effective in causing transmitter release. Transmitter release, and thus postsynaptic conductance, is related to [P]3 (Eq. 3, APPENDIX). 4. We adapted our model to voltage-clamp data gathered at physiological external [Ca2+] (2.0 mM) and tested it for shorter presynaptic voltage steps. Presynaptic Ca2+ currents and synaptic transfer were well simulated under all conditions. 5. The graded synaptic transfer model could be used in a network simulation to reproduce the oscillatory activity of a reciprocally inhibitory pair of heart interneurons. Because synaptic transmission in the model is an explicit function of presynaptic Ca2+ current, the model should prove useful to explore the interaction between membrane currents and synaptic transmission that promote and modulate oscillation in reciprocally inhibitory heart interneurons.