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夹捏电流注入在体外确定了小鼠浅表背角神经元的两种放电模式。

Pinch-current injection defines two discharge profiles in mouse superficial dorsal horn neurones, in vitro.

作者信息

Graham B A, Brichta A M, Callister R J

机构信息

School of Biomedical Sciences, Faculty of Health, The University of Newcastle, Callaghan, NSW 2308, Australia.

出版信息

J Physiol. 2007 Feb 1;578(Pt 3):787-98. doi: 10.1113/jphysiol.2006.123349. Epub 2006 Nov 23.

Abstract

Neurones in the superficial dorsal horn (SDH) are a major target for nociceptive afferents and play an important role in pain processing. One approach to understanding the role of SDH neurones has been to study their action potential (AP) discharge in spinal cord slices during injection of depolarizing step-currents. Four or five neurone subpopulations are typically identified based on AP discharge, with various roles proposed for each in pain processing. During noxious peripheral stimulation in vivo, however, SDH neurones are activated via synaptic inputs. This produces a conductance change with different somato-dendritic distributions and temporal characteristics to that provided by a somatic step-current injection. Here we introduce an alternative approach to studying SDH neurone discharge under in vitro conditions. We recorded voltage-clamp responses in SDH neurones, in vivo, during noxious mechanical stimulation of the hindpaw (1 s pinch, approximately 100 g mm(-2)). From these recordings a representative 'pinch-current' was selected and subsequently injected into SDH neurones in spinal cord slices (recording temperature 32 degrees C). Pinch-current-evoked discharge was compared to that evoked by rectangular step-current injections. Pinch- and step-current-evoked AP discharge frequency was highly correlated (r2 = 0.61). This was also true for rheobase current comparisons (r2 = 0.61). Conversely, latency to discharge and discharge duration were not correlated when step- and pinch-current responses were compared. When neurones were grouped according to step-current-evoked discharge, five distinct patterns were apparent (tonic firing, initial bursting, delayed firing, single spiking, and reluctant firing). In contrast, pinch-current responses separated into two clear patterns of activity (robust and resistant firing). During pinch-current injection, tonic-firing and initial-bursting neurones exhibited robust AP discharge with similar characteristics. In contrast, single-spiking and reluctant-firing neurones were resistant to AP discharge. Delayed-firing neurones exhibited pinch-current responses that were transitional between those of tonic-firing/initial-bursting and single-spiking/reluctant-firing neurones. Injection of digitally filtered pinch-currents indicated that transient current fluctuations are necessary for robust repetitive discharge in initial-bursting neurones. These data suggest the functional significance of the diverse step-current-evoked firing patterns, previously reported in SDH neurones remains to be fully understood. When a 'facsimile' current profile or pinch-current is used in place of step-currents, AP discharge diversity is much reduced.

摘要

脊髓背角浅层(SDH)的神经元是伤害性传入纤维的主要靶点,在疼痛处理中起重要作用。理解SDH神经元作用的一种方法是在脊髓切片中注入去极化阶跃电流时研究其动作电位(AP)发放。通常根据AP发放识别出四到五个神经元亚群,并对每个亚群在疼痛处理中的不同作用提出了各种假设。然而,在体内有害的外周刺激过程中,SDH神经元是通过突触输入被激活的。这会产生一种电导变化,其体-树突分布和时间特征与体细胞阶跃电流注入所产生的不同。在这里,我们介绍一种在体外条件下研究SDH神经元放电的替代方法。我们在体内对后爪进行有害机械刺激(1秒挤压,约100克毫米-2)期间,记录了SDH神经元的电压钳反应。从这些记录中选择一个代表性的“挤压电流”,随后将其注入脊髓切片中的SDH神经元(记录温度32摄氏度)。将挤压电流诱发的放电与矩形阶跃电流注入诱发的放电进行比较。挤压电流和阶跃电流诱发的AP放电频率高度相关(r2 = 0.61)。在基强度电流比较中也是如此(r2 = 0.61)。相反,比较阶跃电流和挤压电流反应时,放电潜伏期和放电持续时间不相关。当根据阶跃电流诱发的放电对神经元进行分组时,出现了五种不同的模式(紧张性发放、初始爆发性发放、延迟发放、单次发放和迟缓发放)。相比之下,挤压电流反应分为两种明显的活动模式(强烈发放和抗性发放)。在注入挤压电流期间,紧张性发放和初始爆发性发放的神经元表现出具有相似特征的强烈AP放电。相比之下,单次发放和迟缓发放的神经元对AP放电具有抗性。延迟发放的神经元表现出的挤压电流反应介于紧张性发放/初始爆发性发放和单次发放/迟缓发放神经元之间。注入数字滤波后的挤压电流表明,瞬态电流波动对于初始爆发性发放神经元的强烈重复放电是必要的。这些数据表明,先前在SDH神经元中报道的不同阶跃电流诱发的发放模式的功能意义仍有待充分理解。当使用“传真式”电流波形或挤压电流代替阶跃电流时,AP放电的多样性会大大降低。

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