Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons
Dendritic spines elongate after stimulation of group 1 metabotropic glutamate receptors in cultured hippocampal neurons
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DOI：
10.1073/pnas.032681099
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发表时间：
2002-02-05
影响因子：
11.1
通讯作者：
Edelman, GM
中科院分区：
文献类型：
--
作者：
Vanderklish, PW;Edelman, GM
树突棘的形态学变化与突触可塑性相关，并可能与其表达和稳定性有关。最近的工作表明，脊柱长度可以通过影响细胞内钙的操作来改变，并且脊柱长度在影响神经元中蛋白质合成的遗传条件下是异常的。我们研究了第1组代谢型谷氨酸受体（mGluRs）的配体如何影响脊柱形状;这些受体的刺激导致钙从细胞内储存释放和树突状蛋白质合成。将培养的海马切片和分离的神经元与选择性第1组mGluR激动剂（S）-3孵育30分钟，5-二羟基苯甘氨酸（DHPG）诱导的树突棘的平均长度显着增加。这种伸长主要是由于现有的棘的生长，也被认为是即使在离子型受体的拮抗剂的存在下，表明这些受体的激活mGluR诱导的谷氨酸释放是不需要的。第1组mGluRs与（S）-α-甲基-4-羧基苯甘氨酸（MCPG）的长期拮抗作用不会导致平均棘长度缩短。DHPG诱导的树突棘的伸长被钙螯合和蛋白质合成抑制剂嘌呤霉素预孵育阻断。结果表明，在体内激活组1 mGluRs的突触释放谷氨酸影响脊柱的形状在蛋白质合成依赖性的方式。
Changes in the morphology of dendritic spines are correlated with synaptic plasticity and may relate mechanistically to its expression and stabilization. Recent work has shown that spine length can be altered by manipulations that affect intracellular calcium, and spine length is abnormal in genetic conditions affecting protein synthesis in neurons. We have investigated how ligands of group 1 metabotropic glutamate receptors (mGluRs) affect spine shape; stimulation of these receptors leads both to calcium release from intracellular stores and to dendritic protein synthesis, Thirty-minute incubation of cultured hippocampal slices and dissociated neurons with the selective group 1 mGluR agonist (S)-3,5-dihydroxyphenylglycine (DHPG) induced a significant increase in the average length of dendritic spines. This elongation resulted mainly from the growth of existing spines and was also seen even in the presence of antagonists of ionotropic receptors, indicating that activation of these receptors by mGluR-induced glutamate release was not required. Prolonged antagonism of group 1 mGluRs with (S)-alpha-methyl-4-carboxyphenylglycine (MCPG) did not result in shorter average spine length. Elongation of dendritic spines induced by DHPG was blocked by calcium chelation and by preincubation with the protein synthesis inhibitor puromycin. The results suggest that in vivo activation of group 1 mGluRs by synaptically released glutamate affects spine shape in a protein synthesis-dependent manner.