Cortical afferents onto the nucleus Reticularis thalami promote plasticity of low-threshold excitability through GluN2C-NMDARs.

Cortical afferents onto the nucleus Reticularis thalami promote plasticity of low-threshold excitability through GluN2C-NMDARs.
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DOI:
10.1038/s41598-017-12552-8
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发表时间:
2017-09-25
期刊:
影响因子:
4.6
通讯作者:
Astori S
Astori S
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Fernandez LMJ;Pellegrini C;Vantomme G;Béard E;Lüthi A;Astori S

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丘脑和大脑皮层是一个高度集成的处理单元,负责详细阐述感觉表征。位于皮层和丘脑之间的丘脑网状核(NRT)接受皮质谷氨酸能强输入,并向丘脑传递自上而下的抑制性反馈。尽管越来越多的人认识到NRT对从睡眠到注意力觉醒的丘脑皮质功能是不可或缺的,但在皮质-NRT通讯和可塑性调节的突触基础上,我们仍然面临着相当大的差距。在这里,我们研究了Ntsr1-Cre x ChR2tg/+小鼠皮质突触驱动对NRT兴奋性的调制,这些小鼠在第6层皮质细胞中表达Channelopoursin2。我们发现皮质-NRT突触表达含有GluN2C亚单位(GluN2C-NMDARs)的大部分NMDA受体。当重复光激活(10 赫兹序列)时,GluN2C-NMDAR诱导NRT兴奋性的长期增加,包括增强T型钙通道的募集。在麻醉的小鼠中,对NRT进行类似的皮质传入刺激会导致皮质局部场电位(LFP)的长期变化,以慢振荡为代价,增量振荡被增强。LFP光谱成分的这种变化对NRT中的NMDAR阻断很敏感。我们的数据揭示了一种新的机制,涉及突触招募的T型钙通道的可塑性修饰和NRT爆发,并表明GluN2C-NMDARs在丘脑皮质节律发生中起关键作用。
Thalamus and cortex represent a highly integrated processing unit that elaborates sensory representations. Interposed between cortex and thalamus, the nucleus Reticularis thalami (nRt) receives strong cortical glutamatergic input and mediates top-down inhibitory feedback to thalamus. Despite growing appreciation that the nRt is integral for thalamocortical functions from sleep to attentional wakefulness, we still face considerable gaps in the synaptic bases for cortico-nRt communication and plastic regulation. Here, we examined modulation of nRt excitability by cortical synaptic drive in Ntsr1-Cre x ChR2tg/+ mice expressing Channelrhodopsin2 in layer 6 corticothalamic cells. We found that cortico-nRt synapses express a major portion of NMDA receptors containing the GluN2C subunit (GluN2C-NMDARs). Upon repetitive photoactivation (10 Hz trains), GluN2C-NMDARs induced a long-term increase in nRt excitability involving a potentiated recruitment of T-type Ca2+ channels. In anaesthetized mice, analogous stimulation of cortical afferents onto nRt produced long-lasting changes in cortical local field potentials (LFPs), with delta oscillations being augmented at the expense of slow oscillations. This shift in LFP spectral composition was sensitive to NMDAR blockade in the nRt. Our data reveal a novel mechanism involving plastic modification of synaptically recruited T-type Ca2+ channels and nRt bursting and indicate a critical role for GluN2C-NMDARs in thalamocortical rhythmogenesis.
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