Department of Neuroscience, Physiology and Pharmacology, University College London, London, UK.
Nat Neurosci. 2011 Oct 9;14(11):1430-8. doi: 10.1038/nn.2942.
Oligodendrocyte precursor cells (OPCs), a major glial cell type that gives rise to myelinating oligodendrocytes in the CNS, express calcium-permeable AMPA receptors (CP-AMPARs). Although CP-AMPARs are important for OPC proliferation and neuron-glia signaling, they render OPCs susceptible to ischemic damage in early development. We identified factors controlling the dynamic regulation of AMPAR subtypes in OPCs from rat optic nerve and mouse cerebellar cortex. We found that activation of group 1 mGluRs drove an increase in the proportion of CP-AMPARs, reflected by an increase in single-channel conductance and inward rectification. This plasticity required the elevation of intracellular calcium and used PI3K, PICK-1 and the JNK pathway. In white matter, neurons and astrocytes release both ATP and glutamate. Unexpectedly, activation of purinergic receptors in OPCs decreased CP-AMPAR expression, suggesting a capacity for homeostatic regulation. Finally, we found that stargazin-related transmembrane AMPAR regulatory proteins, which are critical for AMPAR surface expression in neurons, regulate CP-AMPAR plasticity in OPCs.
少突胶质前体细胞 (OPC) 是一种主要的神经胶质细胞类型，可在中枢神经系统中产生髓鞘形成的少突胶质细胞，表达钙通透性 AMPA 受体 (CP-AMPAR)。尽管 CP-AMPAR 对 OPC 的增殖和神经元-神经胶质信号传递很重要，但它们使 OPC 在早期发育中容易受到缺血损伤。我们鉴定了控制大鼠视神经和小鼠小脑皮质中 OPC 中 AMPAR 亚型动态调节的因素。我们发现，I 组 mGluR 的激活驱动 CP-AMPAR 比例增加，反映在单通道电导和内向整流增加。这种可塑性需要细胞内钙的升高，并利用 PI3K、PICK-1 和 JNK 途径。在白质中，神经元和星形胶质细胞释放 ATP 和谷氨酸。出乎意料的是，OPC 中嘌呤能受体的激活降低了 CP-AMPAR 的表达，表明存在自我平衡调节的能力。最后，我们发现，在神经元中对于 AMPAR 表面表达至关重要的星型胶质相关跨膜 AMPAR 调节蛋白调节 OPC 中的 CP-AMPAR 可塑性。
