Hentall I D, Pinzon A, Noga B R
The Miami Project to Cure Paralysis, University of Miami School of Medicine, P.O. Box 016960, R-48, Miami, FL 33101, USA.
Neuroscience. 2006 Oct 27;142(3):893-903. doi: 10.1016/j.neuroscience.2006.06.038. Epub 2006 Aug 4.
The monoamine neurotransmitter serotonin is released from spinal terminals of nucleus raphe magnus (NRM) neurons and important in sensory and motor control, but its pattern of release has remained unclear. Serotonin was measured by the high-resolution method of fast cyclic voltammetry (2 Hz) with carbon-fiber microelectrodes in lumbar segments (L3-L6) of halothane-anesthetized rats during electrical stimulation of the NRM. Because sites of serotonin release are often histologically remote from membrane transporters and receptors, rapid emergence into aggregate extracellular space was expected. Increased monoamine oxidation currents were found in 94% of trials of 50-Hz, 20-s NRM stimulation across all laminae. The estimated peak serotonin concentration averaged 37.8 nM (maximum 287 nM), and was greater in dorsal and ventral laminae (I-III and VIII-IX) than in intermediate laminae (IV-VI). When measured near NRM-evoked changes, basal monoamine levels (relative to dorsal white matter) were highest in intermediate laminae, while changes in norepinephrine level produced by locus ceruleus (LC) stimulation were lowest in laminae II/III and VII. The NRM-evoked monoamine peak was linearly proportional to stimulus frequency (10-100 Hz). The peak often occurred before the stimulus ended (mean 15.6 s at 50 Hz, range 4-35 s) regardless of frequency, suggesting that release per impulse was constant during the rise but fell later. The latency from stimulus onset to electrochemical signal detection (mean 4.2 s, range 1-23 s) was inversely correlated with peak amplitude and directly correlated with time-to-peak. Quantitative modeling suggested that shorter latencies mostly reflected the time below detection threshold (5-10 nM), so that extrasynaptic serotonin was significantly elevated well within 1 s. Longer latencies (>5 s), which were confined to intermediate laminae, appeared mainly to be due to diffusion from distant sources. In conclusion, except possibly in intermediate laminae, serotonergic volume transmission is a significant mode of spinal control by the NRM.
单胺类神经递质5-羟色胺从中缝大核（NRM）神经元的脊髓终末释放，在感觉和运动控制中起重要作用，但其释放模式尚不清楚。在对氟烷麻醉的大鼠进行NRM电刺激期间，使用碳纤维微电极通过快速循环伏安法（2 Hz）的高分辨率方法测量了腰段（L3-L6）中的5-羟色胺。由于5-羟色胺的释放位点在组织学上通常远离膜转运体和受体，因此预计其会迅速进入聚集的细胞外空间。在所有板层中，50 Hz、20 s的NRM刺激的94%的试验中发现单胺氧化电流增加。估计的5-羟色胺峰值浓度平均为37.8 nM（最大值287 nM），在背侧和腹侧板层（I-III和VIII-IX）中比中间板层（IV-VI）更高。当在NRM诱发的变化附近测量时，基础单胺水平（相对于背侧白质）在中间板层中最高，而蓝斑（LC）刺激引起的去甲肾上腺素水平变化在板层II/III和VII中最低。NRM诱发的单胺峰值与刺激频率（10-100 Hz）呈线性比例关系。无论频率如何，峰值通常在刺激结束前出现（50 Hz时平均为15.6 s，范围为4-35 s），这表明在上升过程中每个冲动的释放是恒定的，但随后下降。从刺激开始到电化学信号检测的潜伏期（平均4.2 s，范围为1-23 s）与峰值幅度呈负相关，与达到峰值的时间呈正相关。定量模型表明，较短的潜伏期主要反映了低于检测阈值（5-10 nM）的时间，因此突触外5-羟色胺在1 s内显著升高。较长的潜伏期（>5 s）局限于中间板层，主要似乎是由于从远处来源扩散所致。总之，除了可能在中间板层外，5-羟色胺能容积传递是NRM对脊髓控制的一种重要模式。
