Pineda J A, Foote S L, Neville H J
Department of Neuroscience, University of California, San Diego, La Jolla 92093.
J Neurosci. 1989 Jan;9(1):81-93. doi: 10.1523/JNEUROSCI.09-01-00081.1989.
It has previously been demonstrated that monkeys exhibit certain event-related potential (ERP) components showing latency, polarity, and contingency similarities to those observed in humans. In the present study, monkey P300-like components were studied in order to evaluate the hypothesis that the noradrenergic locus coeruleus (LC) system participates in their generation or modulation. ERPs were recorded from untrained squirrel monkeys (Saimiri sciureus) twice a week for 4 weeks before and after bilateral LC lesions and interruption of dorsal bundle (DB) fibers. Stimuli consisted of 2 and 6 kHz tone pips (40 msec duration, 60 dB above nHL) presented once a second in random order. In most sessions, one tone constituted 90% of the stimuli and the other tone 10%, while in some sessions tones were made equiprobable to test the effects of manipulating stimulus probability. LC and DB lesions were made by first localizing the nucleus and creating an electrolytic lesion. Then, the electrode was placed at the anterior pole of the nucleus and a knife cut effected. The extent of damage to LC perikarya and ascending axons was assessed by reconstructing lesions from Nissl-stained sagittal sections through the brain stems. The effect of lesions on cortical noradrenergic axons was immunohistochemically verified utilizing antisera directed against dopamine-B-hydroxylase and tyrosine hydroxylase to label noradrenergic and dopaminergic axons, respectively. The prelesion ERP results replicated previous findings of P300-like components recorded in response to low-probability tones. The postlesion ERP data indicated that following damage to LC cell bodies, combined with interruption of histochemically detectable ascending noradrenergic axons, monkey P300-like potentials exhibited decreased areas, altered brain-surface distribution, and reduced sensitivity to stimulus probability. The correlation between the extent of cell body lesions and percentage reduction in the magnitude of P300-like responses was significant. However, interruption of DB fibers alone did not have similar effects. Neither type of lesion had any effect on amplitudes, latencies, or brain-surface distributions of P52, P172, or N250-900. There was, however, a significant effect on N106. Stimulus probability effects on the frontally distributed P52 and N106 were not altered by the lesions. These data support the hypothesis that the integrity of the LC nucleus and its ascending fibers is important in the generation and modulation of surface-recorded P300-like activity.
先前的研究已表明，猴子会表现出某些与事件相关的电位（ERP）成分，这些成分在潜伏期、极性和关联性方面与人类观察到的相似。在本研究中，对猴子的P300样成分进行了研究，以评估去甲肾上腺素能蓝斑（LC）系统参与其产生或调节的假说。在双侧LC损伤和背束（DB）纤维中断前后的4周内，每周两次从未经训练的松鼠猴（松鼠猴）记录ERP。刺激由2千赫和6千赫的短音（持续时间40毫秒，比正常听力水平高60分贝）组成，以随机顺序每秒呈现一次。在大多数实验中，一种音调占刺激的90%，另一种音调占10%，而在一些实验中，两种音调的概率相等，以测试操纵刺激概率的效果。通过首先定位核并制造电解损伤来造成LC和DB损伤。然后，将电极置于核的前极并进行刀切。通过从穿过脑干的尼氏染色矢状切片重建损伤来评估对LC核周体和上升轴突的损伤程度。利用分别针对多巴胺-β-羟化酶和酪氨酸羟化酶的抗血清标记去甲肾上腺素能和多巴胺能轴突，通过免疫组织化学验证损伤对皮质去甲肾上腺素能轴突的影响。损伤前的ERP结果重复了先前关于对低概率音调记录的P300样成分的发现。损伤后的ERP数据表明，在LC细胞体受损并伴有组织化学可检测到的上升去甲肾上腺素能轴突中断后，猴子的P300样电位表现出面积减小、脑表面分布改变以及对刺激概率的敏感性降低。细胞体损伤程度与P300样反应幅度降低百分比之间的相关性显著。然而，单独中断DB纤维并没有类似的效果。两种类型的损伤对P52、P172或N250 - 900的幅度、潜伏期或脑表面分布均无影响。然而，对N106有显著影响。损伤并未改变刺激概率对额叶分布的P52和N106的影响。这些数据支持了这样的假说，即LC核及其上升纤维的完整性在表面记录的P300样活动的产生和调节中很重要。
