Reassessment of the structural basis of the ascending arousal system.
Reassessment of the structural basis of the ascending arousal system.
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DOI：
10.1002/cne.22559
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发表时间：
2011-04-01
影响因子：
2.5
通讯作者：
Lu, Jun
中科院分区：
文献类型：
--
作者：
Fuller, Patrick;Sherman, David;Pedersen, Nigel P.;Saper, Clifford B.;Lu, Jun
“上行网状激活系统”理论提出，上脑干网状结构中的神经元投射到前脑目标，从而促进清醒。最近的研究强调，参与这些通路的脑桥-后脑桥连接处的大多数神经元实际上属于单胺能和胆碱能细胞群。然而，这些细胞群的细胞特异性病变从未能够重现急性旁位中脑病变在中脑尾侧水平横断面上行轴突后所见的深度昏迷。为了确定丘脑皮层传入神经还是基底前脑皮层传入神经在维持觉醒中更重要，我们首先在这些目标中放置了大的细胞体特异性病变。令人惊讶的是，广泛的丘脑病变对脑电图或清醒时的行为测量或清醒时皮质神经元的c-Fos表达几乎没有影响。相比之下，基底前脑损伤较大的动物行为无反应，脑电图单调，低于1 Hz，在连续温和处理期间皮质c-Fos表达很少。然后，我们逆行标记了从上脑干到基底前脑的输入，并在臂旁核和邻近的蓝前区发现了大量来自谷氨酸神经元的输入。臂旁-蓝前复合体的细胞特异性病变产生行为无反应，单调的低于1hz的皮质脑电图，以及在温和处理时皮质c-Fos表达的丧失。这些实验表明，在大鼠中，网状-丘脑-皮质通路可能在行为或皮层电觉醒中发挥非常有限的作用，而来自臂旁核和蓝前区的投射，通过基底前脑传递到大脑皮层，可能对这一过程至关重要。
The “ascending reticular activating system” theory proposed that neurons in the upper brainstem reticular formation projected to forebrain targets that promoted wakefulness. More recent formulations have emphasized that most neurons at the pontomesencepahlic junction that participate in these pathways are actually in monoaminergic and cholinergic cell groups. However, cell-specific lesions of these cell groups have never been able to reproduce the deep coma seen after acute paramedian midbrain lesions that transect ascending axons at the caudal midbrain level. To determine whether the cortical afferents from the thalamus or the basal forebrain were more important in maintaining arousal, we first place large cell-body specific lesions in these targets. Surprisingly, extensive thalamic lesions had little effect on EEG or behavioral measures of wakefulness or on c-Fos expression by cortical neurons during wakefulness. In contrast, animals with large basal forebrain lesions were behaviorally unresponsive, had a monotonous sub-1 Hz EEG, and little cortical c-Fos expression during continuous gentle handling. We then retrogradely labeled inputs to the basal forebrain from the upper brainstem, and found a substantial input from glutamatergic neurons in the parabrachial nucleus and adjacent pre-coeruleus area. Cell specific lesions of the parabrachial-precoeruleus complex produced behavioral unresponsiveness, a monotonous sub-1Hz cortical EEG, and loss of cortical c-Fos expression during gentle handling. These experiments indicate that in rats the reticulo-thalamo-cortical pathway may play a very limited role in behavioral or electrocortical arousal, while the projection from the parabrachial nucleus and precoeruleus region, relayed by the basal forebrain to the cerebral cortex, may be critical for this process.
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