Astrocyte-Secreted Chordin-like 1 Drives Synapse Maturation and Limits Plasticity by Increasing Synaptic GluA2 AMPA Receptors.
Astrocyte-Secreted Chordin-like 1 Drives Synapse Maturation and Limits Plasticity by Increasing Synaptic GluA2 AMPA Receptors.
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DOI：
10.1016/j.neuron.2018.09.043
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发表时间：
2018-12-05
期刊：
影响因子：
16.2
通讯作者：
Allen NJ
中科院分区：
文献类型：
--
作者：
Blanco-Suarez E;Liu TF;Kopelevich A;Allen NJ
在发育中的大脑中，未成熟的突触含有钙可渗透的AMPA谷氨酸受体（AMPAR），随着突触稳定和成熟，AMPAR随后被含GluA 2的钙不可渗透的AMPAR取代。在这里，我们表明，这个重要的开关在AMPAR和神经元突触成熟的星形胶质细胞的调节。利用星形胶质细胞分泌蛋白的生化分离和质谱分析，我们确定星形胶质细胞分泌的chordin like 1（Chrdl 1）是必要的，足以诱导成熟的含GluA 2的突触形成。Chrdl 1的这种功能独立于其作为BMP拮抗剂的作用。Chrdl 1表达仅限于体内皮质星形胶质细胞，在AMPAR开关时达到峰值。在体内可塑性试验中，Chrdl 1 KO小鼠表现出突触GluA 2 AMPAR减少、突触事件动力学改变和重塑增强。研究表明，Chrdl 1突变的人表现出增强的学习能力。因此，星形胶质细胞通过释放Chrdl 1促进GluA 2依赖性突触成熟，从而限制突触可塑性。Blanco-Suarez等人发现，突触成熟不是神经元固有的，而是由邻近的星形胶质细胞调节的。他们证明星形胶质细胞分泌的Chrdl 1增加突触处GluA 2 AMPA受体水平，诱导突触成熟并抑制可塑性。
In the developing brain immature synapses contain calcium-permeable AMPA glutamate receptors (AMPARs) that are subsequently replaced with GluA2-containing calciumimpermeable AMPARs as synapses stabilize and mature. Here we show that this essential switch in AMPARs and neuronal synapse maturation is regulated by astrocytes. Using biochemical fractionation of astrocyte-secreted proteins and mass spectrometry, we identified astrocyte-secreted chordin like 1 (Chrdl1) is necessary and sufficient to induce mature GluA2containing synapses to form. This function of Chrdl1 is independent of its role as an antagonist of BMPs. Chrdl1 expression is restricted to cortical astrocytes in vivo, peaking at the time of the AMPAR switch. Chrdl1 KO mice display reduced synaptic GluA2 AMPARs, altered kinetics of synaptic events, and enhanced remodeling in an in vivo plasticity assay. Studies have shown that humans with mutations in Chrdl1 display enhanced learning. Thus astrocytes, via the release of Chrdl1, promote GluA2-dependent synapse maturation, and thereby limit synaptic plasticity. Blanco-Suarez et al. identify that synapse maturation is not intrinsic to neurons, but is regulated by neighboring astrocytes. They demonstrate that astrocyte-secreted Chrdl1 increases GluA2 AMPA receptor levels at synapses, inducing synapse maturation and inhibiting plasticity.
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影响因子：
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作者：
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DOI：
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发表时间：
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期刊：
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