Neurophysiological analysis of sleep regulation mechanism through the basal ganglion-pontine tegmental systems

脑桥被盖区在REM睡眠和觉醒的调节中起着至关重要的作用。基底神经节投射到脑桥被盖区，参与运动调节或肌肉紧张的调节。下丘脑中的食欲素能系统投射到基底神经节（黑质网状部：SNr）或脑桥被盖，并调节睡眠和觉醒期间的各种事件。本研究旨在阐明下丘脑-基底节轴介导的睡眠调节机制，特别是与肌张力调节的关系。得到的结果是：1.在去神经猫，注射食欲素激活SNr可增加或维持肌张力水平，电刺激脚桥被盖核（PPN）引起的肌张力减弱在SNr注射食欲素后被抑制。GABA_A受体拮抗剂荷包牡丹碱（bicuculline）可阻断增食欲素的作用。当将食欲素注射到PPN时，获得了相同的效果。提示SNr内GABA能神经元或PPN内GABA能中间神经元通过抑制启动肌张力的PPN神经元来调节肌张力。2.在自由活动大鼠的PPN内注射orexin后，微透析法测定GABA释放量增加。实验结果支持了PPN神经元的紧张性GABA能抑制的假说，这种抑制是由食欲素能影响SNr或PPN神经元介导的。这些神经元是GABA能输入到PPN的候选者，其在觉醒期间抑制PPN中的张力缺乏诱导系统。

The pontine tegmental area has a crucial role in regulation of REM sleep and wakefulness. The basal ganglia is, projecting to the pontine tegmental area, involved in motor regulation or regulation of muscular tonus. The orexinergic system in the hypothalamus project to the basal ganglia (substantia nigra pars reticulata : SNr) or the pontine tegmentum and regulate the various events during sleep and wakefulness. The present study was performed to elucidate the sleep regulation mechanisms especially the relation of muscular tonus regulation mediated by the hypothalamic-basal ganglia axis. The results obtained are ;1.In decebrated cats, activation of the SNr by orexin injection increased or maintained the muscular tonus level ; muscular atonia induced by the electrical stimulation to the pedunculopontine tegmental nucleus (PPN) was suppressed after the orexin injection to the SNr. The orexin effect was blocked by bicuculline (GABA_A receptor antagonist). The same effect was obtained when orexin was injected to the PPN. These results suggest that the GABAergic neurons in the SNr or the GABAergic interneurons in the PPN regulate the muscular tonus by suppressing the PPN neurons that initiate muscular atonia.2.When orexin was injected to the PPN in free moving rats, GABA release measured by microdialysis method increased. The result supports the hypothesis that the there is a tonic GABAergic inhibition on the PPN neurons that is mediated by the orexinergic influence to the SNr or PPN.3.The GABAergic neurons in the SNr showed higher activity during wakefulness or bpoth wakefulness and REM sleep. These neurons are candidates of the GABAergic input to the PPN that suppress the atonia inducing system in the PPN during wakefulness.