Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation.
Astrocytes modulate thalamic sensory processing via mGlu2 receptor activation.
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DOI：
10.1016/j.neuropharm.2017.04.019
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发表时间：
2017-07-15
影响因子：
4.7
通讯作者：
Salt TE
中科院分区：
文献类型：
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作者：
Copeland CS;Wall TM;Sims RE;Neale SA;Nisenbaum E;Parri HR;Salt TE
星形胶质细胞拥有许多与神经元相同的信号分子。然而，星形胶质细胞在信息处理中的作用，如果有的话，是未知的。利用电生理和成像方法，我们报告了星形胶质细胞调节啮齿动物丘脑神经元感觉抑制的第一个证据。我们发现mGlu2受体活性降低了从丘脑网状核到体感腹基底丘脑（VB）的抑制传递：II组mGlu受体激动剂LY354740降低了VB片中的mIPSC频率，mGlu2阳性变构调节剂（PAM） LY487379共同应用增强了这一作用（30 nM LY354740: 10.0±1.6%；30 nM LY354740和30 μM LY487379: 34.6±5.2%）。然后，我们在星形胶质细胞上发现了mGlu2受体的激活：II组激动剂提高了星形胶质细胞内钙水平，mGlu2 - PAM共应用后，钙水平进一步增强（300 nM LY354740：比值幅度0.016±0.002；300 nM LY354740和30 μ LY487379：比值幅度0.035±0.003）。然后，我们在体内证明了mGlu2依赖性星形细胞对VB神经元的去抑制作用：II组激动剂和mGlu2 PAM （LY354740: 156±12%的对照组；LY487379: 144±10%的对照组）解除了VB神经元对振动刺激序列的反应。胶质细胞抑制剂氟柠檬酸盐的存在消除了mGlu2 PAM效应（对照组的91±5%），表明II组效应的mGlu2成分可归因于位于VB内星形细胞过程的mGlu2受体的激活。星形胶质细胞激活的丘脑皮质功能门控是一种新的感觉加工机制。由于这种丘脑皮质回路在鉴别过程中很重要，这证明了星形胶质细胞在突触过程中潜在的注意和认知的重要性。丘脑抑制是由神经元和星形细胞机制介导的。II组mGlu受体（mGlu2/3）的激活可以调节这种丘脑抑制。mGlu2受体刺激可激活丘脑星形胶质细胞。这个过程可以使相关的活动从背景噪音中辨别出来。因此，靶向星形细胞mGlu2受体可能会影响注意力和认知。
Astrocytes possess many of the same signalling molecules as neurons. However, the role of astrocytes in information processing, if any, is unknown. Using electrophysiological and imaging methods, we report the first evidence that astrocytes modulate neuronal sensory inhibition in the rodent thalamus. We found that mGlu2 receptor activity reduces inhibitory transmission from the thalamic reticular nucleus to the somatosensory ventrobasal thalamus (VB): mIPSC frequencies in VB slices were reduced by the Group II mGlu receptor agonist LY354740, an effect potentiated by mGlu2 positive allosteric modulator (PAM) LY487379 co-application (30 nM LY354740: 10.0 ± 1.6% reduction; 30 nM LY354740 & 30 μM LY487379: 34.6 ± 5.2% reduction). We then showed activation of mGlu2 receptors on astrocytes: astrocytic intracellular calcium levels were elevated by the Group II agonist, which were further potentiated upon mGlu2 PAM co-application (300 nM LY354740: ratio amplitude 0.016 ± 0.002; 300 nM LY354740 & 30 μM LY487379: ratio amplitude 0.035 ± 0.003). We then demonstrated mGlu2-dependent astrocytic disinhibition of VB neurons in vivo: VB neuronal responses to vibrissae stimulation trains were disinhibited by the Group II agonist and the mGlu2 PAM (LY354740: 156 ± 12% of control; LY487379: 144 ± 10% of control). Presence of the glial inhibitor fluorocitrate abolished the mGlu2 PAM effect (91 ± 5% of control), suggesting the mGlu2 component to the Group II effect can be attributed to activation of mGlu2 receptors localised on astrocytic processes within the VB. Gating of thalamocortical function via astrocyte activation represents a novel sensory processing mechanism. As this thalamocortical circuitry is important in discriminative processes, this demonstrates the importance of astrocytes in synaptic processes underlying attention and cognition. Thalamic inhibition is mediated by both neuronal and astrocytic mechanisms. Group II mGlu receptor (mGlu2/3) activation can modulate this thalamic inhibition. Thalamic astrocytes can be activated upon mGlu2 receptor stimulation. This process may enable relevant activity to be discerned from background noise. Targeting astrocytic mGlu2 receptors may therefore affect attention and cognition.