Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, QC, Canada.
Neuroscience. 2010 Sep 1;169(3):1150-7. doi: 10.1016/j.neuroscience.2010.06.003. Epub 2010 Jun 9.
Orexin (Orx or hypocretin) is critically important for maintaining wakefulness, since in its absence, narcolepsy with cataplexy occurs. In this role, Orx-containing neurons can exert their influence upon multiple targets through the brain by release of Orx but possibly also by release of other neurotransmitters. Indeed, evidence was previously presented to suggest that Orx terminals could utilize glutamate (Glu) in addition to Orx as a neurotransmitter. Using fluorescence and confocal laser scanning microscopy, we investigated whether Orx varicosities contain the presynaptic markers for synaptic release of Glu or GABA and come into contact with postsynaptic markers for excitatory synapses within the locus coeruleus of the rat brain. We found that a proportion of the Orx+ varicosities were immunostained for the vesicular transporter for Glu, VGluT2. None were immunostained for vesicular glutamate transporter 1 (VGluT1) or VGluT3 or for the vesicular transporter for GABA, vesicular GABA transporter (VGAT). Among the Orx+ varicosities, 4% of all and 28% of large varicosities contained VGluT2. A similar proportion of the large Orx+ varicosities contained synaptophysin (Syp), a presynaptic marker for synaptic vesicles. Orx+ varicosities also contacted elements immunostained for postsynaptic density protein-95 (PSD)-95, a postsynaptic marker for glutamatergic synapses. We thus conclude that synaptic release of Glu occurs from Orx terminals within the locus coeruleus and can thus be important for the engagement of noradrenergic neurons in stimulating and maintaining arousal.
食欲素（Orx 或下丘脑泌素）对于维持清醒状态至关重要，因为在其缺失的情况下，会发生伴有猝倒的发作性睡病。在这个角色中，含有食欲素的神经元可以通过释放食欲素来影响大脑中的多个靶点，但也可能通过释放其他神经递质来发挥作用。事实上，之前有证据表明，食欲素末梢可以利用谷氨酸（Glu）作为神经递质，除了食欲素之外。使用荧光和共聚焦激光扫描显微镜，我们研究了食欲素囊泡是否包含 Glu 或 GABA 突触释放的突触前标记物，并与大鼠蓝斑内兴奋性突触的突触后标记物接触。我们发现，一部分 Orx+ 囊泡被 Glu 的囊泡转运体，VGluT2 免疫染色。没有被囊泡谷氨酸转运体 1（VGluT1）、VGluT3 或 GABA 的囊泡转运体，囊泡 GABA 转运体（VGAT）免疫染色。在 Orx+ 囊泡中，所有囊泡的 4%和大囊泡的 28%含有 VGluT2。同样比例的大 Orx+ 囊泡含有突触小体蛋白（Syp），这是突触小泡的突触前标记物。Orx+ 囊泡也与突触后密度蛋白-95（PSD-95）免疫染色的元素接触，PSD-95 是谷氨酸能突触的突触后标记物。因此，我们得出结论，Glu 的突触释放发生在蓝斑内的食欲素末梢，因此对于去甲肾上腺素能神经元参与刺激和维持觉醒非常重要。
