Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada, and National Institute on Drug Abuse, Neuronal Networks Section, National Institutes of Health, Baltimore, Maryland 21224.
J Neurosci. 2014 Mar 26;34(13):4708-27. doi: 10.1523/JNEUROSCI.2617-13.2014.
Distributed within the laterodorsal tegmental and pedunculopontine tegmental nuclei (LDT and PPT), cholinergic neurons in the pontomesencephalic tegmentum have long been thought to play a critical role in stimulating cortical activation during waking (W) and paradoxical sleep (PS, also called REM sleep), yet also in promoting PS with muscle atonia. However, the discharge profile and thus precise roles of the cholinergic neurons have remained uncertain because they lie intermingled with GABAergic and glutamatergic neurons, which might also assume these roles. By applying juxtacellular recording and labeling in naturally sleeping-waking, head-fixed rats, we investigated the discharge profiles of histochemically identified cholinergic, GABAergic, and glutamatergic neurons in the LDT, SubLDT, and adjoining medial part of the PPT (MPPT) in relation to sleep-wake states, cortical activity, and muscle tone. We found that all cholinergic neurons were maximally active during W and PS in positive correlation with fast (γ) cortical activity, as "W/PS-max active neurons." Like cholinergic neurons, many GABAergic and glutamatergic neurons were also "W/PS-max active." Other GABAergic and glutamatergic neurons were "PS-max active," being minimally active during W and maximally active during PS in negative correlation with muscle tone. Conversely, some glutamatergic neurons were "W-max active," being maximally active during W and minimally active during PS in positive correlation with muscle tone. Through different discharge profiles, the cholinergic, GABAergic, and glutamatergic neurons of the LDT, SubLDT, and MPPT thus appear to play distinct roles in promoting W and PS with cortical activation, PS with muscle atonia, or W with muscle tone.
在脑桥被盖和脚桥被盖核(LDT 和 PPT)内分布的中脑被盖背外侧核和脚桥核的胆碱能神经元,长期以来一直被认为在刺激清醒(W)和异相睡眠(PS,也称为 REM 睡眠)期间的皮质激活方面发挥着关键作用,但也在促进 PS 时肌肉弛缓中发挥作用。然而,由于它们与 GABA 能和谷氨酸能神经元交织在一起,这些神经元也可能承担这些作用,因此,胆碱能神经元的放电模式及其确切作用仍然不确定。通过在自然睡眠-觉醒、头部固定的大鼠中应用细胞外记录和标记,我们研究了 LDT、SubLDT 和毗邻的中脑被盖脚桥核内侧部(MPPT)中组织化学鉴定的胆碱能、GABA 能和谷氨酸能神经元的放电模式与睡眠-觉醒状态、皮质活动和肌肉张力的关系。我们发现,所有的胆碱能神经元在 W 和 PS 期间都处于最大活性,与快速(γ)皮质活动呈正相关,被称为“W/PS-最大活性神经元”。与胆碱能神经元类似,许多 GABA 能和谷氨酸能神经元也是“W/PS-最大活性”。其他 GABA 能和谷氨酸能神经元是“PS-最大活性”,在 W 期间活动最少,在 PS 期间活动最多,与肌肉张力呈负相关。相反,一些谷氨酸能神经元是“W-最大活性”,在 W 期间活动最大,在 PS 期间活动最小,与肌肉张力呈正相关。通过不同的放电模式,LDT、SubLDT 和 MPPT 的胆碱能、GABA 能和谷氨酸能神经元似乎在促进皮质激活的 W 和 PS、PS 时肌肉弛缓或 W 时肌肉张力方面发挥着不同的作用。