Synaptic Channel Modeling for DMC: Neurotransmitter Uptake and Spillover in the Tripartite Synapse
Synaptic Channel Modeling for DMC: Neurotransmitter Uptake and Spillover in the Tripartite Synapse
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DOI：
10.1109/tcomm.2020.3040318
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发表时间：
2020-05
影响因子：
8.3
通讯作者：
Sebastian Lotter;Arman Ahmadzadeh;R. Schober
中科院分区：
文献类型：
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作者：
Sebastian Lotter;Arman Ahmadzadeh;R. Schober
在扩散分子通信（DMC）中，信息通过扩散分子来传输。突触信号，作为这种范式的自然实现，包括功能组件，一旦理解，可以促进合成DMC系统的发展。然而，为了释放这种潜力，需要基于生物物理学原理对突触通信通道进行彻底的理解。由于突触传递也严重依赖于非神经细胞，这种理解需要考虑所谓的三重突触。在本文中，我们开发了一个全面的通道模型的三方突触，包括一个三维的，有限大小的空间模型的突触间隙，分子摄取在突触前神经元和神经胶质细胞，可逆结合到单个受体在突触后神经元，和溢出的突触外空间。基于这个模型，我们推导出解析时域表达式的通道脉冲响应（CIR）的突触DMC系统和突触前神经元和神经胶质细胞，分别采取的分子数量。这些表达式提供了洞察宏观物理通道参数的CIR和再摄取率的衰减速率的影响，并揭示了化学反应动力学和通道几何形状诱导的突触信号传输的基本限制。适应现实的参数，我们的模型产生合理的结果相比，以前的实验和模拟研究，我们提供了基于粒子的计算机模拟的结果，以进一步验证分析模型。建议的全面通道模型承认广泛的突触配置，使其适合于调查的许多实际相关的问题，如神经胶质细胞的摄取和溢出信号传输的影响，在三方突触。
In Diffusive Molecular Communication (DMC), information is transmitted by diffusing molecules. Synaptic signaling, as a natural implementation of this paradigm, encompasses functional components that, once understood, can facilitate the development of synthetic DMC systems. To unleash this potential, however, a thorough understanding of the synaptic communication channel based on biophysical principles is needed. Since synaptic transmission critically depends also on non-neural cells, such understanding requires the consideration of the so-called tripartite synapse. In this paper, we develop a comprehensive channel model of the tripartite synapse encompassing a three-dimensional, finite-size spatial model of the synaptic cleft, molecule uptake at the presynaptic neuron and at glial cells, reversible binding to individual receptors at the postsynaptic neuron, and spillover to the extrasynaptic space. Based on this model, we derive analytical time domain expressions for the channel impulse response (CIR) of the synaptic DMC system and for the number of molecules taken up at the presynaptic neuron and at glial cells, respectively. These expressions provide insight into the impact of macroscopic physical channel parameters on the decay rate of the CIR and the reuptake rate, and reveal fundamental limits for synaptic signal transmission induced by chemical reaction kinetics and the channel geometry. Adapted to realistic parameters, our model produces plausible results when compared to previous experimental and simulation studies and we provide results from particle-based computer simulations to further validate the analytical model. The proposed comprehensive channel model admits a wide range of synaptic configurations making it suitable for the investigation of many practically relevant questions, such as the impact of glial cell uptake and spillover on signal transmission in the tripartite synapse.