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首页> 外文期刊>Brain structure & function >Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes
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Endocannabinoid signaling modulates neurons of the pedunculopontine nucleus (PPN) via astrocytes

机译：内源性大麻素信号传导通过星形胶质细胞调节人足桥核（PPN）的神经元

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The pedunculopontine nucleus (PPN) is known as the cholinergic part of the reticular activating system (RAS) and it plays an important role in transitions of slow-wave sleep to REM sleep and wakefulness. Although both exogenous and endocannabinoids affect sleep, the mechanism of endocannabinoid neuromodulation has not been characterized at cellular level in the PPN. In this paper, we demonstrate that both neurons and glial cells from the PPN respond to cannabinoid type 1 (CB1) receptor agonists. The neuronal response can be depolarization or hyperpolarization, while astrocytes exhibit more frequent calcium waves. All these effects are absent in CB1 gene-deficient mice. Blockade of the fast synaptic neurotransmission or neuronal action potential firing does not change the effect on the neuronal membrane potential significantly, while inhibition of astrocytic calcium waves by thapsigargin diminishes the response. Inhibition of group I metabotropic glutamate receptors (mGluRs) abolishes hyperpolarization, whereas blockade of group II mGluRs prevents depolarization. Initially active neurons and glial cells display weaker responses partially due to the increased endocannabinoid tone in their environment. Taken together, we propose that cannabinoid receptor stimulation modulates PPN neuronal activity in the following manner: active neurons may elicit calcium waves in astrocytes via endogenous CB1 receptor agonists. Astrocytes in turn release glutamate that activates different metabotropic glutamate receptors of neurons and modulate PPN neuronal activity.
机译：足桥骨核（PPN）被称为网状激活系统（RAS）的胆碱能部分，在慢波睡眠向REM睡眠和清醒的过渡中起着重要作用。尽管外源性和内源性大麻素均会影响睡眠，但内源性大麻素神经调节的机制尚未在PPN的细胞水平上得到表征。在本文中，我们证明了PPN的神经元和神经胶质细胞均对1型大麻素（CB1）受体激动剂起反应。神经元反应可以是去极化或超极化，而星形胶质细胞表现出更频繁的钙波。在CB1基因缺陷小鼠中没有所有这些作用。快速突触神经传递或神经元动作电位放电的阻滞不会明显改变对神经元膜电位的影响，而毒胡萝卜素对星形胶质钙波的抑制会减少反应。对I组代谢型谷氨酸受体（mGluRs）的抑制作用消除了超极化作用，而对II组mGluRs的阻断作用则阻止了去极化作用。最初活跃的神经元和神经胶质细胞显示出较弱的反应，部分原因是其环境中内源性大麻素的含量增加。两者合计，我们建议大麻素受体刺激以下列方式调节PPN神经元的活动：活跃的神经元可能通过内源性CB1受体激动剂在星形胶质细胞中引起钙波。星形胶质细胞继而释放谷氨酸，谷氨酸激活神经元的不同代谢型谷氨酸受体并调节PPN神经元活性。

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