Multiple interacting sites of ectopic spike electrogenesis in primary sensory neurons

Multiple interacting sites of ectopic spike electrogenesis in primary sensory neurons
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DOI:
10.1523/jneurosci.4118-04.2005
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发表时间:
2005-03-09
影响因子:
5.3
通讯作者:
Devor, M
Devor, M
中科院分区:
医学1区
文献类型:
--
作者:
Amir, R;Kocsis, JD;Devor, M

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损伤的传入轴突和细胞体在体内产生的异位放电是神经损伤后慢性感觉障碍和疼痛的重要原因。已经取得了进展,了解负责这种放电的过程中使用的准备组成的整个切除的背根神经节(DRG)与切断的神经连接。然而,在体外制备中,尖峰活动起源于DRG细胞索马,但很少在轴突。我们现在已经克服了这个障碍,了解整体的生电过程中索马和轴突,包括由此产生的放电模式,通过修改浴介质中进行记录。在这两个部位,爆发都可以由阈下振荡、相位刺激或神经元其他部位出现的尖峰触发。在索马中,一旦触发,爆发由去极化后电位维持,而在轴突中,一个额外的过程也起作用,延迟去极化电位。这种替代过程似乎涉及“时钟样”爆发,放电模式更常见于轴突比胞体。异位棘波交替出现在索马、受损轴突末端(神经瘤)和轴突T连接区。放电序列,甚至单个多重峰爆发,可能是起源于神经元内这些替代性生电位点的动作电位的马赛克。相应地,在这些替代站点产生的放电可能相互作用,解释了在体内观察到的有时复杂的放电模式。
Ectopic discharge generated in injured afferent axons and cell somata in vivo contributes significantly to chronic neuropathic dysesthesia and pain after nerve trauma. Progress has been made toward understanding the processes responsible for this discharge using a preparation consisting of whole excised dorsal root ganglia (DRGs) with the cut nerve attached. In the in vitro preparation, however, spike activity originates in the DRG cell soma but rarely in the axon. We have now overcome this impediment to understanding the overall electrogenic processes in soma and axon, including the resulting discharge patterns, by modifying the bath medium in which recordings are made. At both sites, bursts can be triggered by subthreshold oscillations, a phasic stimulus, or spikes arising elsewhere in the neuron. In the soma, once triggered, bursts are maintained by depolarizing afterpotentials, whereas in the axon, an additional process also plays a role, delayed depolarizing potentials. This alternative process appears to be involved in "clock-like" bursting, a discharge pattern much more common in axons than somata. Ectopic spikes arise alternatively in the soma, the injured axon end ( neuroma), and the region of the axonal T-junction. Discharge sequences, and even individual multiplet bursts, may be a mosaic of action potentials that originate at these alternative electrogenic sites within the neuron. Correspondingly, discharge generated at these alternative sites may interact, explaining the sometimes-complex firing patterns observed in vivo.