Comparison of Properties of Brainstem Cholinergic and Noradrenergic Neurons in Vivo and in Vitro

1)在乌拉坦麻醉的大鼠被盖外侧背侧核(LDT)细胞外记录到两种动作电位，即“短峰”和“宽峰”，以峰的宽度区分清楚。后者与蓝斑(LC)去甲肾上腺素能神经元或中缝背核(DR)5-羟色胺能神经元产生的棘波非常相似。投射到前脑部位的LDT神经元大多有宽棘波，解剖学证据表明宽棘波神经元是胆碱能神经元。2)在体外脑干切片制作中，LDT神经元可记录到宽棘波。(为了在下面的实验中集中我们的精力，我们不能进一步进行这个实验)3)为了阐明中脑桥胆碱能神经元作为激活系统的组成部分的功能作用，未用药的大鼠，头部无痛固定的LDT中的单个神经元活动是r…。与皮质脑电和颈部肌电一起记录的更多。还记录了部分LC和DR神经元的活动以供比较。大多数动物都被剥夺了24小时的睡眠。只对产生宽峰的神经元进行了观察，从以前的研究中得知，这是胆碱能或单胺能的。4)根据觉醒(AW)、慢波睡眠(SWS)和异相睡眠(PS)时的放电频率，将LDT内的46个宽峰神经元分为四组：I)AW期间最活跃的神经元，PS期间最安静的神经元(其中一些可能是5-羟色胺能神经元，而不是胆碱能神经元，因为LC中的10个神经元和DR中的9个神经元基本上都是5-羟色胺能神经元)；Iii)AW和PS期间神经元同样比SWS更活跃；以及iv)其他主要特征是唤醒和/或PS开始时的一过性促进活动。组II和组III的神经元是LDT的主要成分，这两组神经元约占LDT神经元的40%。在大多数神经元中，放电的变化早于脑电变化，但从PS中觉醒时除外。5)感觉刺激，如轻触尾巴或吹气，在一些神经元中只是在较高警戒水平下诱发放电状态，而在另一些神经元中，感觉刺激引起习惯性的时相反应。6)本研究和其他研究结果表明：1)LDT由具有与睡眠/觉醒(和感觉反应)相关的异质性特征的胆碱能神经元组成，大多数在PS或PS和AW中表现出高活性；以及ii)一些被盖胆碱能神经元在PS、PS和AW的诱导和维持中起关键作用。同时在与意识相关的提升激活中只起到很小的作用。较少

1) Two kinds of action potentials (spikes) were recorded extracellularly in the laterodorsal tegmental nucleus (LDT) of the rat anesthetized with urethane, that is "brief spikes" and "broad spikes" , distinguished clearly with width of spikes. The latter were very similar to spikes generated by noradrenergic neurons of the locus coeruleus (LC) or serotonergic neurons of the dorsal raphe nucleus (DR). The majority of LDT neurons projecting to the forebrain sites had broad spikes, which, with an anatomical evidence, suggests that the broad-spike neurons are cholinergic.2) The broad spikes could be recorded intracellularly from LDT neurons in in vitro slice preparation of the brainstem. (We could not perform this experiment further in order to concentrate our efforts in the below experiments.)3) To clarify functional roles of mesopontine cholinergic neurons as a component of an activating system, single neuronal activity in the LDT of undrugged rats, whose head was fixed painlessly, was r … More ecorded along with cortical EEG and neck EMG. Activity of some LC and DR neurons was also recorded for comparison. Most of animals had been sleep-deprived for 24 hours. Observation was made only on neurons generating broad spikes, known from previous studies to be cholinergic or monoaminergic. The position of recorded neurons was marked by pontamine sky blue ejected from the glass pipette microelectrode, and was identified on sections processed for NADPH diaphorase histochemistry which stained cholinergic neurons specifically.4) According to their firing rates during wakefulness (AW), slow wave sleep (SWS) and paradoxical sleep (PS), 46 broad-spike neurons in the LDT were classified into four groups : i) neurons most active during AW and silent during PS (some of these neurons might be serotonergic rather than cholinergic, as substantially all of 10 neurons in the LC and 9 neurons in the DR) ; ii) neurons most active during PS and silent during AW ; iii) neurons equally more active during AW and PS than SWS ; and iv) others mainly characterized by transiently facilitated activity at awaking and/or onset of PS. Neurons of groups ii and iii were the main constituent of the LDT, either group populating about 40% of the LDT neurons. In most neurons change in firing preceded EEG change, except at awaking from PS.5) Sensory stimulation such as light touch to the tail or air puff to the face simply induced a state of firing during higher vigilance levels in some neurons, while in others the sensory stimulation evoked phasic responses habituated by repetition.6) The results of the present and other studies suggest that i) the LDT is composed of cholinergic neurons with heterogenous characteristics in relation to sleep/wakefulness (and also to sensory responses), the majority displaying heightened activity in PS or in PS and AW, and ii) some tegmental cholinergic neurons play a pivotal role in induction and maintenance of PS, while having but a minor role in the ascending activation relevant to consciousness. Less