Mohns Ethan J, Karlsson Karl A E, Blumberg Mark S
Program in Behavioral and Cognitive Neuroscience, Department of Psychology, University of Iowa, Iowa City, 52242, USA.
Eur J Neurosci. 2006 Mar;23(5):1301-10. doi: 10.1111/j.1460-9568.2006.04652.x.
Recent findings in infant rats suggest that the preoptic area (POA) and/or basal forebrain (BF) contribute to developmental changes in sleep and wake organization between postnatal day 2 (P2) and P9. To examine the contributions of these forebrain areas to sleep and wakefulness, separate lesions of the POA or BF, or combined lesions (POA + BF), were performed at P9, and precollicular transections were performed at P2. In addition, modafinil, a drug of unknown mechanism of action the effects of which on sleep and wakefulness have been hypothesized to result from inhibition of POA activity, was administered at P2 and P9. Finally, extracellular neuronal activity was recorded from the POA and BF. POA lesions decreased sleep bout durations and increased wake bout durations. BF lesions inhibited sleep bout durations to a lesser extent, while leaving wake bout durations unaffected. POA + BF lesions produced a combination of these effects, resulting in short bouts of sleep and wakefulness similar to those of transected P8 rats. Even at P2, transections decreased sleep bout durations. The finding, however, that the sleep-inhibiting and wake-promoting effects of modafinil were more potent at P9 than at P2 suggests increasing sleep-wake modulation by the POA between these two ages. Finally, neuronal recordings confirmed the presence of state-dependent neurons within the infant POA and BF. We propose that the POA, in addition to promoting sleep, inhibits wakefulness via direct and indirect inhibitory connections with wake-promoting neurons in the BF, and that this inhibitory influence increases across early development.
近期对幼鼠的研究发现表明，视前区（POA）和/或基底前脑（BF）在出生后第2天（P2）至P9期间对睡眠和觉醒组织的发育变化有影响。为了研究这些前脑区域对睡眠和觉醒的作用，在P9时分别对POA或BF进行损伤，或进行联合损伤（POA + BF），并在P2时进行视交叉前横断。此外，在P2和P9时给予莫达非尼，这是一种作用机制不明的药物，其对睡眠和觉醒的影响被认为是通过抑制POA活性产生的。最后，记录了POA和BF的细胞外神经元活动。POA损伤缩短了睡眠周期时长，增加了觉醒周期时长。BF损伤对睡眠周期时长的抑制作用较小，而对觉醒周期时长没有影响。POA + BF联合损伤产生了这些效应的组合，导致睡眠和觉醒周期短暂，类似于P8横断大鼠的情况。即使在P2时，横断也会缩短睡眠周期时长。然而，莫达非尼的促觉醒和抑制睡眠作用在P9时比在P2时更强，这一发现表明在这两个年龄段之间POA对睡眠-觉醒的调节作用增强。最后，神经元记录证实了幼鼠POA和BF中存在状态依赖性神经元。我们提出，POA除了促进睡眠外，还通过与BF中促觉醒神经元的直接和间接抑制性连接来抑制觉醒，并且这种抑制作用在早期发育过程中会增强。
