Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons
Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons
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DOI：
10.1152/jn.00755.2011
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发表时间：
2012-03-01
影响因子：
2.5
通讯作者：
Liu, S. J.
中科院分区：
文献类型：
--
作者：
Dubois, C. J.;Ramamoorthy, P.;Liu, S. J.
Dubois CJ，Ramamoorthy P，Whim MD，Liu SJ. NPY 5型受体的激活诱导小脑抑制性中间神经元自发GABA释放的长期持续增加。J Neurophysiol 107：1655-1665，2012.首次发表于2011年12月21日; doi：10.1152/jn.00755.2011.-神经肽Y（neuropeptide Y，NPY）是一种广泛分布于中枢神经系统的神经肽，可分别通过Y2和Y1受体（Y2 rs和Y1 rs）短暂抑制抑制性突触传递，改变膜兴奋性。虽然许多GABA能神经元表达Y 5 rs，但这些受体在抑制性神经元中的功能作用尚不清楚。在这里，我们调查是否激活Y 5 rs可以调节抑制性传输小脑切片。出乎意料的是，应用神经肽Y引发了长期持续的增加，在星状细胞的微型抑制性突触后电流的频率。NPY还诱导培养的小脑神经元自发GABA释放持续增加。当小脑培养物进行检查Y 5 r免疫反应，染色共定位与VGAT，GABA能细胞的突触前标记，表明Y 5 rs位于突触前抑制性神经元的终端。RT-PCR实验证实了小脑中Y 5 r mRNA的存在。NPY诱导的GABA释放增强被Y 5 r拮抗剂阻断，并通过应用Y 5 r的选择性肽激动剂来模拟。因此，Y 5 r激活是必要的，足以触发GABA释放的增加。最后，抑制传输的增强不能被逆转的Y 5 R拮抗剂一旦启动，与发展的长期增强。这些结果表明，激活突触前Y 5 RS诱导持续增加的自发GABA释放抑制性神经元的抑制性传输的特征是Y1 R和Y2 R激活的瞬时抑制相反。因此，我们的研究结果揭示了一种新的作用，突触前Y 5 RS抑制性中间神经元在调节GABA的释放，并建议这些受体可以发挥作用，在小脑神经元网络活动的塑造。
Dubois CJ, Ramamoorthy P, Whim MD, Liu SJ. Activation of NPY type 5 receptors induces a long-lasting increase in spontaneous GABA release from cerebellar inhibitory interneurons. J Neurophysiol 107: 1655-1665, 2012. First published December 21, 2011; doi:10.1152/jn.00755.2011.-Neuropeptide Y (NPY), a widely distributed neuropeptide in the central nervous system, can transiently suppress inhibitory synaptic transmission and alter membrane excitability via Y2 and Y1 receptors (Y2rs and Y1rs), respectively. Although many GABAergic neurons express Y5rs, the functional role of these receptors in inhibitory neurons is not known. Here, we investigated whether activation of Y5rs can modulate inhibitory transmission in cerebellar slices. Unexpectedly, application of NPY triggered a long-lasting increase in the frequency of miniature inhibitory postsynaptic currents in stellate cells. NPY also induced a sustained increase in spontaneous GABA release in cultured cerebellar neurons. When cerebellar cultures were examined for Y5r immunoreactivity, the staining colocalized with that of VGAT, a presynaptic marker for GABAergic cells, suggesting that Y5rs are located in the presynaptic terminals of inhibitory neurons. RT-PCR experiments confirmed the presence of Y5r mRNA in the cerebellum. The NPY-induced potentiation of GABA release was blocked by Y5r antagonists and mimicked by application of a selective peptide agonist for Y5r. Thus Y5r activation is necessary and sufficient to trigger an increase in GABA release. Finally, the potentiation of inhibitory transmission could not be reversed by a Y5r antagonist once it was initiated, consistent with the development of a long-term potentiation. These results indicate that activation of presynaptic Y5rs induces a sustained increase in spontaneous GABA release from inhibitory neurons in contrast to the transient suppression of inhibitory transmission that is characteristic of Y1r and Y2r activation. Our findings thus reveal a novel role of presynaptic Y5rs in inhibitory interneurons in regulating GABA release and suggest that these receptors could play a role in shaping neuronal network activity in the cerebellum.