Rukhadze I, Fenik V B, Branconi J L, Kubin L
Department of Animal Biology 209E/VET, School of Veterinary Medicine and Center for Sleep and Respiratory Neurobiology, University of Pennsylvania, 3800 Spruce Street, Philadelphia, PA 19104-6046, USA.
Neuroscience. 2008 Mar 3;152(1):208-22. doi: 10.1016/j.neuroscience.2007.11.013.
Pontine noradrenergic neurons of the locus coeruleus (LC) and sub-coeruleus (SubC) region cease firing during rapid eye movement sleep (REMS). This plays a permissive role in the generation of REMS and may contribute to state-dependent modulation of transmission in the CNS. Whether all pontomedullary catecholaminergic neurons, including those in the A1/C1, A2/C2 and A7 groups, have REMS-related suppression of activity has not been tested. We used Fos protein expression as an indirect marker of the level of neuronal activity and linear regression analysis to determine whether pontomedullary cells identified by tyrosine hydroxylase (TH) immunohistochemistry have reduced Fos expression following REMS-like state induced by pontine microinjections of a cholinergic agonist, carbachol in urethane-anesthetized rats. The percentage of Fos-positive TH cells was negatively correlated with the cumulative duration of REMS-like episodes induced during 140 min prior to brain harvesting in the A7 and rostral A5 groups bilaterally (P < 0.01 for both), and in SubC neurons on the side opposite to carbachol injection (P < 0.05). Dorsal medullary A2/C2 neurons did not exhibit such correlation, but their Fos expression (and that in A7, rostral A5 and SubC neurons) was positively correlated with the duration of the interval between the last REMS-like episode and the time of perfusion (P < 0.05). In contrast, neither of these correlations was significant for A1 /C1 or caudal A5 neurons. These findings suggest that, similar to the prototypic LC neurons, neurons of the A7, rostral A5 and A2/C2 groups have reduced or abolished activity during REMS, whereas A1 /IC1 and caudal A5 neurons do not have this feature. The reduced activity of A2/C2, A5 and A7 neurons during REMS, and the associated decrements in norepinephrine release, may cause state-dependent modulation of.transmission in brain somato- and viscerosensory, somatomotor, and cardiorespiratory pathways.
蓝斑(LC)和蓝斑下(SubC)区域的脑桥去甲肾上腺素能神经元在快速眼动睡眠(REMS)期间停止放电。这在REMS的产生中起允许作用,并可能有助于中枢神经系统中与状态相关的传递调节。包括A1/C1、A2/C2和A7组中的那些神经元在内的所有脑桥延髓儿茶酚胺能神经元是否具有与REMS相关的活动抑制尚未得到测试。我们使用Fos蛋白表达作为神经元活动水平的间接标记,并通过线性回归分析来确定经酪氨酸羟化酶(TH)免疫组织化学鉴定的脑桥延髓细胞在经脑桥微量注射胆碱能激动剂卡巴胆碱在乌拉坦麻醉大鼠中诱导出类似REMS状态后是否Fos表达降低。双侧A7和吻侧A5组中,Fos阳性TH细胞的百分比与在脑收获前140分钟内诱导的类似REMS发作的累积持续时间呈负相关(两者均P < 0.01),并且在卡巴胆碱注射对侧的SubC神经元中也是如此(P < 0.05)。延髓背侧A2/C2神经元未表现出这种相关性,但其Fos表达(以及A7、吻侧A5和SubC神经元中的表达)与最后一次类似REMS发作与灌注时间之间的间隔持续时间呈正相关(P < 0.05)。相比之下,对于A1/C1或尾侧A5神经元,这些相关性均不显著。这些发现表明,与典型的LC神经元类似,A7、吻侧A5和A2/C2组的神经元在REMS期间活动减少或消失,而A1/IC1和尾侧A5神经元不具有此特征。A2/C2、A5和A7神经元在REMS期间活动的减少以及去甲肾上腺素释放的相关减少,可能导致大脑躯体和内脏感觉、躯体运动以及心肺呼吸通路中与状态相关的传递调节。