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首页> 外文期刊>The European Journal of Neuroscience >Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons.
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Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons.

机译：食欲素B / hypocretin 2增加谷氨酸能传递到腹侧被盖区神经元。

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摘要

The orexins (hypocretins) play a crucial role in arousal, feeding and reward. Highly relevant to these functions, orexin-containing neurons from the lateral hypothalamus project densely to the ventral tegmental area (VTA), which is the origin of dopamine projections implicated in motivation and reward. Orexin A/hypocretin 1 (oxA/hcrt-1) can enable long-term changes associated with drugs of abuse; however, the effects of orexin B/hypocretin 2 (oxB/hcrt-2) on excitatory synaptic transmission in the VTA are unknown. We used whole-cell patch-clamp electrophysiology in rat horizontal midbrain slices to examine the effects of oxB/hcrt-2 on excitatory synaptic transmission. We observed that oxB/hcrt-2 has distinct effects from oxA/hcrt-1 in the VTA. oxB/Hcrt-2 (100 nm) increased presynaptic glutamate release in addition to a postsynaptic potentiation of NMDA receptors (NMDARs). The oxB/hcrt-2-mediated postsynaptic potentiation of NMDARs was mediated via activation of orexin/hypocretin 2 (OX2/Hcrt-2) receptorsand protein kinase C (PKC). Furthermore, the increase in transmitter release probability was also PKC-dependent, but not through activation of orexin/hypocretin 1 (OX1/Hcrt-1) or OX2/Hcrt-2 receptors. Finally, oxB/hcrt-2 or the selective OX2/Hcrt-2 receptor agonist ala(11)-d-leu(15)-orexin B, significantly reduced spike-timing-induced long-term potentiation. Taken together, these results support a dual role for oxB/hcrt-2 in mediating enhanced glutamatergic transmission in the VTA, and suggest that oxA/hcrt-1 and oxB/hcrt-2 exert different functional roles in modulating the enhancement of the motivational components of arousal and feeding.
机译：食欲素（hypocretins）在唤醒，喂养和奖励中起着至关重要的作用。与这些功能高度相关的是，来自下丘脑外侧的含orexin的神经元密集地投射到腹侧被盖区（VTA），这是多巴胺投射的起源，与动机和奖励有关。 Orexin A / hypocretin 1（oxA / hcrt-1）可使与滥用药物有关的长期变化成为可能;但是，尚不清楚orexin B / hypocretin 2（oxB / hcrt-2）对VTA中兴奋性突触传递的影响。我们在大鼠水平中脑切片中使用全细胞膜片钳电生理检查了oxB / hcrt-2对兴奋性突触传递的影响。我们观察到oxB / hcrt-2在VTA中具有与oxA / hcrt-1不同的作用。除NMDA受体（NMDARs）的突触后增强作用外，oxB / Hcrt-2（100 nm）还增加了突触前谷氨酸的释放。 oxB / hcrt-2介导的NMDAR突触后增强是通过激活orexin / hypocretin 2（OX2 / Hcrt-2）受体和蛋白激酶C（PKC）介导的。此外，递质释放概率的增加也是PKC依赖性的，但不是通过orexin / hypocretin 1（OX1 / Hcrt-1）或OX2 / Hcrt-2受体的激活来实现的。最后，oxB / hcrt-2或选择性OX2 / Hcrt-2受体激动剂ala（11）-d-leu（15）-毒素B显着降低了穗定时诱导的长期增强作用。综上所述，这些结果支持oxB / hcrt-2在介导VTA中增强的谷氨酸能传递中起双重作用，并表明oxA / hcrt-1和oxB / hcrt-2在调节动力成分的增强中发挥不同的功能作用。唤醒和喂养。

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