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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Hypocretin/orexin innervation and excitation of identified septohippocampal cholinergic neurons.
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Hypocretin/orexin innervation and excitation of identified septohippocampal cholinergic neurons.

机译:降钙素/食欲神经支配和确定的海马胆碱能神经元的兴奋。

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摘要

Hypothalamic fibers containing the wake-promoting peptides, hypocretins (Hcrts) or orexins, provide a dense innervation to the medial septum-diagonal band of Broca (MSDB), a sleep-associated brain region that has been suggested to show intense axonal degeneration in canine narcoleptics. The MSDB, via its cholinergic and GABAergic projections to the hippocampus, controls the hippocampal theta rhythm and associated learning and memory functions. Neurons of the MSDB express very high levels of the Hcrt receptor 2, which is mutated in canine narcoleptics. In the present study, we investigated the electrophysiological effects of Hcrt peptides on septohippocampal cholinergic neurons that were identified in living brain slices of the MSDB using a selective fluorescent marker. Hcrt activation of septohippocampal cholinergic neurons was reversible, reproducible, and concentration dependent and mediated via a direct postsynaptic mechanism. Both Hcrt1 and Hcrt2 activated septohippocampal cholinergic neurons with similar EC(50) values. The Hcrt effect was dependent on external Na(+), reduced by external Ba(2+), and also reduced in recordings with CsCl-containing electrodes, suggesting a dual underlying ionic mechanism that involved inhibition of a K(+) current, presumably an inward rectifier, and a Na(+)-dependent component. The Na(+) component was dependent on internal Ca(2+), blocked by replacing external Na(+) with Li(+), and also blocked by bath-applied Ni(2+) and KB-R7943, suggesting involvement of the Na(+)-Ca(2+) exchanger. Using double-immunolabeling studies at light and ultrastructural levels, we also provide definitive evidence for a hypocretin innervation of cholinergic neurons. Thus Hcrt effects within the septum should increase hippocampal acetylcholine release and thereby promote hippocampal arousal.
机译:下丘脑纤维含有促唤醒肽,降钙素(Hcrts)或orexins,为Broca的中隔中隔对角带(MSDB)提供密集的神经支配,Broca是与睡眠有关的大脑区域,已被证明在犬中表现出强烈的轴突变性麻醉药。 MSDB通过其对海马的胆碱能和GABA能预测,控制海马theta节律以及相关的学习和记忆功能。 MSDB的神经元表达非常高水平的Hcrt受体2,而Hcrt受体2在犬麻醉药中会发生突变。在本研究中,我们调查了Hcrt肽对隔海马胆碱能神经元的电生理作用,该海马胆碱能神经元是使用选择性荧光标记在MSDB的活脑切片中鉴定的。隔海马胆碱能神经元的Hcrt激活是可逆的,可重现的和浓度依赖性的,并通过直接的突触后机制介导。 Hcrt1和Hcrt2都激活具有相似EC(50)值的海马胆碱能神经元。 Hcrt效应取决于外部Na(+),通过外部Ba(2+)降低,并且在含CsCl电极的记录中也降低,提示可能涉及抑制K(+)电流的双重潜在离子机制。一个向内整流器和一个依赖Na(+)的组件。 Na(+)组件取决于内部Ca(2+),通过用Li(+)代替外部Na(+)来阻止,并且也被镀浴的Ni(2+)和KB-R7943阻止,这表明Na(+)-Ca(2+)交换剂。在轻度和超微结构水平上使用双重免疫标记研究,我们还为胆碱能神经元的降钙素神经支配提供了确凿的证据。因此,隔膜中的Hcrt效应应增加海马乙酰胆碱的释放,从而促进海马唤醒。

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