Webster H H, Jones B E
Department of Psychology, McGill University, Montreal, Qué., Canada.
Brain Res. 1988 Aug 23;458(2):285-302. doi: 10.1016/0006-8993(88)90471-4.
Kainic acid was injected bilaterally (4.8 micrograms in 1.2 microliters each side) into the dorsolateral pontomesencephalic tegmentum of cats in order to destroy the cholinergic neurons located in that region and thus to study the effects of their destruction upon sleep-waking states. The kainic acid produced a large area of nerve cell loss and/or gliosis centered in the dorsolateral tegmentum-cholinergic cell area, that includes the pedunculopontine tegmental (PPT) and laterodorsal tegmental (LDT) nuclei rostrally (A1-P2), and the parabrachial (PB) and locus coeruleus (LC) nuclei caudally (P3-P5). The mean loss of choline acetyltransferase (ChAT)-immunoreactive neurons within this area was 60% with a range from 25% to 85% across 11 cats. The mean loss of tyrosine hydroxylase (TH)-immunoreactive neurons, differentially distributed through the same region, was 35% with a range of 0-50%. Whereas the kainic acid lesions appeared to have only slight effects upon wakefulness and slow-wave sleep, they had marked effects upon paradoxical sleep (PS), which varied in degree across animals. In cats with the most extensive destruction of cholinergic neurons, PS was eliminated in the first few weeks following the lesion and then reappeared as isolated episodes characterized by sparse, low amplitude PGO spikes in association with few eye movements and an activated cortex, though in absence of neck muscle atonia. Although these PS-like episodes varied in amount, they were significantly less than baseline PS in percent and in duration for the group of 11 animals over one month recording. The PGO spike rate was significantly reduced; the EMG amplitude was significantly increased, marking a loss of neck muscle atonia. The percent of PS-like epochs, the rate of PGO spiking and the EMG amplitude on postlesion day 28 were found to be significantly correlated with the volume of the lesion within the dorsolateral pontine tegmentum-cholinergic cell area. The percent PS-like episodes and PGO spike rate were significantly correlated with the number of remaining ChAT-immunoreactive neurons, but not with the number of remaining TH-immunoreactive neurons within this region. These results suggest that cholinergic pontomesencephalic neurons may be critically involved in the generation of paradoxical sleep and its phasic events.
向猫的双侧背外侧脑桥中脑被盖区注射海藻酸（每侧1.2微升中含4.8微克），以破坏位于该区域的胆碱能神经元，从而研究其破坏对睡眠-觉醒状态的影响。海藻酸导致以背外侧被盖胆碱能细胞区为中心的大面积神经细胞丢失和/或胶质细胞增生，该区域包括吻侧的脚桥被盖（PPT）和背外侧被盖（LDT）核（A1-P2），以及尾侧的臂旁（PB）核和蓝斑（LC）核（P3-P5）。该区域内胆碱乙酰转移酶（ChAT）免疫反应性神经元的平均丢失率为60%，11只猫的范围为25%至85%。酪氨酸羟化酶（TH）免疫反应性神经元在同一区域分布不同，平均丢失率为35%，范围为0-50%。虽然海藻酸损伤对觉醒和慢波睡眠似乎只有轻微影响，但对异相睡眠（PS）有显著影响，不同动物的影响程度有所不同。在胆碱能神经元破坏最广泛的猫中，PS在损伤后的头几周消失，然后重新出现，表现为孤立的发作，其特征是与少量眼球运动和激活的皮层相关的稀疏、低幅PGO波峰，尽管此时颈部肌肉无张力缺失。虽然这些类似PS的发作数量各不相同，但在11只动物一个月的记录中，它们在百分比和持续时间上均显著低于基线PS。PGO波峰率显著降低；肌电图振幅显著增加，表明颈部肌肉无张力缺失。发现在损伤后第28天，类似PS的时段百分比、PGO波峰发放率和肌电图振幅与背外侧脑桥被盖胆碱能细胞区内的损伤体积显著相关。类似PS的发作百分比和PGO波峰率与该区域内剩余的ChAT免疫反应性神经元数量显著相关，但与剩余的TH免疫反应性神经元数量无关。这些结果表明，脑桥中脑胆碱能神经元可能在异相睡眠及其相位事件的产生中起关键作用。
