Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons
Orexin B/hypocretin 2 increases glutamatergic transmission to ventral tegmental area neurons
复制标题
DOI：
10.1111/j.1460-9568.2008.06397.x
复制
发表时间：
2008-10-01
影响因子：
3.4
通讯作者：
Bonci, A.
中科院分区：
文献类型：
--
作者：
Borgland, S. L.;Storm, E.;Bonci, A.
食欲素（hypocretins）在唤醒，进食和奖励中起着至关重要的作用。与这些功能高度相关的是，下丘脑外侧含有食欲素的神经元密集地投射到腹侧被盖区（VTA），这是与动机和奖励有关的多巴胺投射的起源。食欲素A/下丘脑泌素1（oxA/hcrt-1）可导致与药物滥用相关的长期变化;然而，食欲素B/下丘脑泌素2（oxB/hcrt-2）对腹侧被盖区兴奋性突触传递的影响尚不清楚。我们采用大鼠水平中脑脑片全细胞膜片钳电生理检查oxB/hcrt-2对兴奋性突触传递的影响。我们观察到oxB/hcrt-2与oxA/hcrt-1在腹侧被盖区有不同的作用。oxB/Hcrt-2（100 nM）除了增加NMDA受体（NMDAR）的突触后增强作用外，还增加了突触前谷氨酸的释放。oxB/hcrt-2介导的NMDAR的突触后增强作用是通过激活食欲素/下丘脑泌素2（OX 2/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，但不是通过激活食欲素/下丘脑泌素1（OX 1/Hcrt-1）或OX 2/Hcrt-2受体。最后，oxB/hcrt-2或选择性OX 2/Hcrt-2受体激动剂ala（11）-D-leu（15）-食欲素B显著降低尖峰定时诱导的长时程增强。两者合计，这些结果支持oxB/hcrt-2在介导增强腹侧被盖区中的兴奋性传递中的双重作用，并表明oxA/hcrt-1和oxB/hcrt-2在调节唤醒和进食的动机成分的增强中发挥不同的功能作用。
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) receptors and 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.