Ionic mechanisms underlying tonic and burst firing behavior in subfornical organ neurons: a combined experimental and modeling study
Ionic mechanisms underlying tonic and burst firing behavior in subfornical organ neurons: a combined experimental and modeling study
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DOI：
10.1152/jn.00340.2018
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发表时间：
2018-11-01
影响因子：
2.5
通讯作者：
Ferguson, Alastair, V
中科院分区：
文献类型：
--
作者：
Medlock, Laura;Shute, Lauren;Ferguson, Alastair, V
穹窿下器（SFO）神经元在电流表达和尖峰发放行为上表现出异质性，其中两种主要的尖峰发放表型表现为强直性和爆发性放电。深入了解这种异质性背后的机制对于理解SFO（一种感觉性室周器官）如何发挥作用至关重要。整合并选择性地影响生理功能。为了整合有效的方法来研究这种异质性，我们建立了一个单室。通过SFO特异性体外膜片钳数据参数化的SFO神经元的Hodgkin-Huxley型模型。该模型占紧张性和爆发性放电SFO神经元的膜电位分布和尖峰序列的变异性。模型动力学分析证实，持续的Na+和Ca 2+电流需要爆发的启动和维护，并表明，慢激活的K+电流可能是负责在SFO神经元的爆发终止。此外，该模型表明，电流表达的异质性和随后对尖峰后电位的影响是紧张性和爆发性放电SFO神经元之间行为差异的基础。未来使用该模型与单神经元膜片钳电生理学的协调，为解释和预测SFO神经元对循环信号的各种组合的反应提供了一个平台。因此阐明了SFO内生理信号整合的潜在机制。新&值得注意的是，我们对穹窿下器官（SFO）如何选择性地影响自主神经系统功能的理解仍然不完全，但理论上是SFO神经元对生理重要信号的电响应的结果。我们已经建立了一个计算模型的SFO神经元，来自实验数据和支持。这解释了SFO神经元如何产生不同的电模式。该模型提供了一个有效的系统，从理论上和实验上探索SFO神经元的基本特征的变化如何影响其电活动。
Subfornical organ (SFO) neurons exhibit heterogeneity in current expression and spiking behavior, where the two major spiking phenotypes appear as tonic and burst firing. Insight into the mechanisms behind this heterogeneity is critical for understanding how the SFO, a sensory circumventricular organ. integrates and selectively influences physiological function. To integrate efficient methods for studying this heterogeneity, we built a single-compartment. Hodgkin-Huxley-type model of an SFO neuron that is parameterized by SFO-specific in vitro patch-clamp data. The model accounts for the membrane potential distribution and spike train variability of both tonic and burst firing SFO neurons. Analysis of model dynamics confirms that a persistent Na+ and Ca2+ currents are required for burst initiation and maintenance and suggests that a slow-activating K+ current may be responsible for burst termination in SFO neurons. Additionally, the model suggests that heterogeneity in current expression and subsequent influence on spike afterpotential underlie the behavioral differences between tonic and burst firing SFO neurons. Future use of this model in coordination with single neuron patch-clamp electrophysiology provides a platform for explaining and predicting the response of SFO neurons to various combinations of circulating signals. thus elucidating the mechanisms underlying physiological signal integration within the SFO.NEW & NOTEWORTHY Our understanding of how the subfornical organ (SFO) selectively influences autonomic nervous system function remains incomplete but theoretically results from the electrical responses of SFO neurons to physiologically important signals. We have built a computational model of SFO neurons, derived from and supported by experimental data. which explains how SFO neurons produce different electrical patterns. The model provides an efficient system to theoretically and experimentally explore how changes in the essential features of SFO neurons affect their electrical activity.