Dramatically Amplified Thoracic Sympathetic Postganglionic Excitability and Integrative Capacity Revealed with Whole-Cell Patch-Clamp Recordings.
Dramatically Amplified Thoracic Sympathetic Postganglionic Excitability and Integrative Capacity Revealed with Whole-Cell Patch-Clamp Recordings.
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DOI：
10.1523/eneuro.0433-18.2019
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发表时间：
2019-03-01
期刊：
影响因子：
3.4
通讯作者：
Hochman, Shawn
中科院分区：
文献类型：
--
作者：
McKinnon, Michael Lee;Tian, Kun;Hochman, Shawn
胸椎旁交感节后神经元（tSPN）包括控制血管和体温调节系统的分布式交感神经系统的最终整合输出。被认为是一个非整合中继，什么是知之甚少的tSPN内在兴奋性已确定尖锐的微电极与假定刺穿损伤。因此，我们进行了tSPN细胞特性的第一个电生理学表征，使用全细胞记录和耦合结果与基于电导的模型，探索其兴奋性的原则，在成年小鼠的两种性别。记录的膜电阻和时间常数值比以前获得的值大一个数量级，导致突触整合在驾驶招聘的可证明的能力。膜电阻率的变化是控制细胞兴奋性的主要决定因素，tSPN募集所需的电流大大降低。与先前在小鼠中观察到无法维持放电的微电极记录不同，所有tSPN都能够重复放电。计算模型表明，所观察到的差异解释了微电极穿刺损伤电导的引入。总的来说，tSPN在很大程度上线性编码注入电流幅度在一个广泛的频率范围内与不同的亚群可区分的基础上重复的点火签名。因此，全细胞记录显示tSPN具有比以前认为的更显著放大的兴奋性，具有更大的突触整合的内在能力，并且具有维持放电以支持对血管紧张素和体温调节功能的持续作用的能力。而不是作为一个中继，这些研究支持一个更敏感的作用和可能的内在能力tSPN驱动交感神经自主功能。
Thoracic paravertebral sympathetic postganglionic neurons (tSPNs) comprise the final integrative output of the distributed sympathetic nervous system controlling vascular and thermoregulatory systems. Considered a non-integrating relay, what little is known of tSPN intrinsic excitability has been determined by sharp microelectrodes with presumed impalement injury. We thus undertook the first electrophysiological characterization of tSPN cellular properties using whole-cell recordings and coupled results with a conductance-based model to explore the principles governing their excitability in adult mice of both sexes. Recorded membrane resistance and time constant values were an order of magnitude greater than values previously obtained, leading to a demonstrable capacity for synaptic integration in driving recruitment. Variation in membrane resistivity was the primary determinant controlling cell excitability with vastly lower currents required for tSPN recruitment. Unlike previous microelectrode recordings in mouse which observed inability to sustain firing, all tSPNs were capable of repetitive firing. Computational modeling demonstrated that observed differences are explained by introduction of a microelectrode impalement injury conductance. Overall, tSPNs largely linearly encoded injected current magnitudes over a broad frequency range with distinct subpopulations differentiable based on repetitive firing signatures. Thus, whole-cell recordings reveal tSPNs have more dramatically amplified excitability than previously thought, with greater intrinsic capacity for synaptic integration and with the ability for maintained firing to support sustained actions on vasomotor tone and thermoregulatory function. Rather than acting as a relay, these studies support a more responsive role and possible intrinsic capacity for tSPNs to drive sympathetic autonomic function.