Maloney K J, Mainville L, Jones B E
Department of Neurology and Neurosurgery, McGill University, Montreal Neurological Institute, Montreal, Quebec, H3A 2B4, Canada.
J Neurosci. 1999 Apr 15;19(8):3057-72. doi: 10.1523/JNEUROSCI.19-08-03057.1999.
Multiple lines of evidence indicate that neurons within the pontomesencephalic tegmentum are critically involved in the generation of paradoxical sleep (PS). From single-unit recording studies, evidence suggests that unidentified but "possibly" cholinergic tegmental neurons discharge at higher rates during PS than during slow wave sleep or even waking and would thus play an active role, whereas "presumed" monoaminergic neurons cease firing during PS and would thus play a permissive role in PS generation. In the present study performed on rats, c-Fos immunostaining was used as a reflection of neuronal activity and combined with immunostaining for choline acetyltransferase (ChAT), serotonin (Ser), tyrosine hydroxylase (TH), or glutamic acid decarboxylase (GAD) for immunohistochemical identification of active neurons during PS recovery ( approximately 28% of recording time) as compared with PS deprivation (0%) and PS control (approximately 15%) conditions. With PS recovery, there was a significant increase in ChAT+/c-Fos+ cells, a significant decrease in Ser+/c-Fos+ and TH+/c-Fos+ cells, and a significant increase in GAD+/c-Fos+ cells. Across conditions, the percent PS was correlated positively with tegmental cholinergic c-Fos+ cells, negatively with raphe serotonergic and locus coeruleus noradrenergic c-Fos+ cells, and positively with codistributed and neighboring GABAergic c-Fos+ cells. These results support the hypothesis that cholinergic neurons are active, whereas monoaminergic neurons are inactive during PS. They moreover indicate that GABAergic neurons are active during PS and could thus be responsible for inhibiting neighboring monoaminergic neurons that may be essential in the generation of PS.
多条证据表明,脑桥中脑被盖区内的神经元在异相睡眠(PS)的产生中起关键作用。从单单位记录研究来看,有证据表明,身份不明但“可能”为胆碱能的被盖神经元在PS期间的放电频率高于慢波睡眠甚至清醒时,因此可能发挥积极作用,而“推测”为单胺能的神经元在PS期间停止放电,因此可能在PS产生中起许可作用。在本项针对大鼠的研究中,c-Fos免疫染色被用作神经元活动的反映,并与胆碱乙酰转移酶(ChAT)、5-羟色胺(Ser)、酪氨酸羟化酶(TH)或谷氨酸脱羧酶(GAD)的免疫染色相结合,以便在PS恢复(记录时间的约28%)期间对活跃神经元进行免疫组织化学鉴定,并与PS剥夺(0%)和PS对照(约15%)条件进行比较。随着PS恢复,ChAT+/c-Fos+细胞显著增加,Ser+/c-Fos+和TH+/c-Fos+细胞显著减少,GAD+/c-Fos+细胞显著增加。在所有条件下,PS百分比与被盖胆碱能c-Fos+细胞呈正相关,与中缝5-羟色胺能和蓝斑去甲肾上腺素能c-Fos+细胞呈负相关,与共分布和相邻的GABA能c-Fos+细胞呈正相关。这些结果支持了以下假设:胆碱能神经元在PS期间活跃,而单胺能神经元不活跃。此外,它们还表明GABA能神经元在PS期间活跃,因此可能负责抑制可能对PS产生至关重要的相邻单胺能神经元。