Melanin-Concentrating Hormone Neurons Release Glutamate for Feedforward Inhibition of the Lateral Septum
Melanin-Concentrating Hormone Neurons Release Glutamate for Feedforward Inhibition of the Lateral Septum
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DOI：
10.1523/jneurosci.4187-14.2015
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发表时间：
2015-02-25
影响因子：
5.3
通讯作者：
Maratos-Flier, Eleftheria
中科院分区：
文献类型：
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作者：
Chee, Melissa J. S.;Arrigoni, Elda;Maratos-Flier, Eleftheria
黑色素浓缩激素（MCH）调节重要的生理功能，包括能量平衡和睡眠。MCH细胞被认为是GABA能细胞，释放GABA抑制下游靶标。然而，很少有实验支持这种范式。为了更好地了解小鼠MCH神经元的突触机制，我们进行了神经解剖图谱和表征，然后进行了光遗传学测试，以测试它们在下游靶点的功能连接。突触素介导的投影图谱显示，间隔外侧核（LS）中MCH神经末梢的聚集最为密集。然后，我们在MCH神经元中表达通道视紫红质-2，并光刺激MCH投射，以确定它们对LS活性的影响。MCH投射的光刺激引起LS的单突触谷氨酸释放。有趣的是，这导致了一种前馈抑制，通过强大的次级GABA释放来抑制LS放电。本研究通过MCH和LS神经元之间的电路分析，证实了它们在单突触和多突触通路上的功能联系。我们的研究结果表明，MCH神经元并非完全具有gaba能，并揭示了谷氨酸介导的前馈抑制LS细胞的机制。
Melanin-concentrating hormone (MCH) regulates vital physiological functions, including energy balance and sleep. MCH cells are thought to be GABAergic, releasing GABA to inhibit downstream targets. However, there is little experimental support for this paradigm. To better understand the synaptic mechanisms of mouse MCH neurons, we performed neuroanatomical mapping and characterization followed by optogenetics to test their functional connectivity at downstream targets. Synaptophysin-mediated projection mapping showed that the lateral septal nucleus (LS) contained the densest accumulation of MCH nerve terminals. We then expressed channelrhodopsin-2 in MCH neurons and photostimulated MCH projections to determine their effect on LS activity. Photostimulation of MCH projections evoked a monosynaptic glutamate release in the LS. Interestingly, this led to a feedforward inhibition that depressed LS firing by a robust secondary GABA release. This study presents a circuit analysis between MCH and LS neurons and confirms their functional connection via monosynaptic and polysynaptic pathways. Our findings indicate that MCH neurons are not exclusively GABAergic and reveal a glutamate-mediated, feedforward mechanism that inhibits LS cells.