Yamamoto K, Mamelak A N, Quattrochi J J, Hobson J A
Department of Psychiatry, Harvard Medical School, Boston, MA 02115.
Neuroscience. 1990;39(2):279-93. doi: 10.1016/0306-4522(90)90267-8.
Carbachol, a long-acting cholinergic agonist, was microinjected (4 micrograms/250 nl per 90 s) into 90 sites within the anterodorsal pontine tegmentum of four cats and the time to onset and percentage of time spent in a desynchronized sleep-like state during 40 min postinjection were calculated. Compared with more posteroventral pontine sites, the shorter latencies and higher percentages observed confirmed earlier predictions of a sensitive cholinoceptive zone in the anterodorsal pons. In 27 trials a desynchronized sleep-like state was observed within 5 min; in 31 trials the latency was 5-10 min and in the remaining 32 trials, greater than 10 min. Plotting the desynchronized sleep-like state latency and the desynchronized sleep-like state percentage as a function of the three-dimensional coordinates revealed that injection sites with short latency (less than 5 min) and high percentage (greater than 80%) were concentrated between the coordinates of P 1.0 to 3.5 and V -3.5 to -5.5, at the lateral coordinate L 2.0. On the frontal plane, the short desynchronized sleep-like state latency and high desynchronized sleep-like state percentage sites begin in the pontine tegmental region just lateral to the ventral tegmental nucleus and extend 3 mm ventrocaudally. A regression plot of the data in sagittal plane 2.0 revealed a short latency axis, around which the short latency sites cluster, running in a slightly dorsoventral direction from about P 1.0 to V -4.0 to P 4.0 to V -5.5. This observation suggests that the sensitive zone might approximate a cylinder in shape, a hypothesis supported by the correlation of longer latencies and lower percentages at increasing radial distance from the axis. The non-linear relationship between cholinergic potency and distance from the short latency axis suggests that the desynchronized sleep-like state latency is a function of two factors; a variable diffusion-based delay of carbachol to distant neuronal populations involved in the desynchronized sleep-like state production, and a fixed recruitment-based delay following activation of neurons in the sensitive zone. Interpretation of these findings in light of earlier studies involving microstimulation of the pontine tegmentum argue in favor of a distributed network of discrete neuronal populations as the source of desynchronized sleep generation.
将长效胆碱能激动剂卡巴胆碱（每90秒4微克/250纳升）微量注射到4只猫的脑桥前背侧被盖区内的90个位点，并计算注射后40分钟内进入去同步化睡眠样状态的起始时间和持续时间百分比。与脑桥后腹侧的位点相比，观察到的较短潜伏期和较高百分比证实了早期关于脑桥前背侧存在敏感胆碱能感受区的预测。在27次试验中，在5分钟内观察到去同步化睡眠样状态；在31次试验中，潜伏期为5 - 10分钟，其余32次试验中潜伏期大于10分钟。将去同步化睡眠样状态潜伏期和去同步化睡眠样状态百分比作为三维坐标的函数进行绘图显示，潜伏期短（小于5分钟）且百分比高（大于80%）的注射位点集中在P 1.0至3.5和V -3.5至-5.5的坐标之间，横向坐标为L 2.0。在额平面上，去同步化睡眠样状态潜伏期短且百分比高的位点始于腹侧被盖核外侧的脑桥被盖区，并向腹尾侧延伸3毫米。矢状面2.0上的数据回归图显示了一个短潜伏期轴，短潜伏期位点围绕该轴聚集，从大约P 1.0至V -4.0到P 4.0至V -5.5呈略微背腹方向延伸。这一观察结果表明，敏感区可能近似圆柱形，这一假设得到了随着与轴的径向距离增加潜伏期延长和百分比降低的相关性的支持。胆碱能效力与距短潜伏期轴的距离之间的非线性关系表明，去同步化睡眠样状态潜伏期是两个因素的函数；卡巴胆碱向参与去同步化睡眠样状态产生的远处神经元群体扩散的可变延迟，以及敏感区内神经元激活后的固定募集延迟。根据早期涉及脑桥被盖微刺激的研究对这些发现进行解释，支持了离散神经元群体的分布式网络是去同步化睡眠产生源的观点。
