5-HT7R/G12 signaling regulates neuronal morphology and function in an age-dependent manner.
5-HT7R/G12 signaling regulates neuronal morphology and function in an age-dependent manner.
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DOI：
10.1523/jneurosci.2765-11.2012
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发表时间：
2012-02-29
期刊：
影响因子：
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通讯作者：
Ponimaskin E
中科院分区：
文献类型：
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作者：
Kobe F;Guseva D;Jensen TP;Wirth A;Renner U;Hess D;Müller M;Medrihan L;Zhang W;Zhang M;Braun K;Westerholz S;Herzog A;Radyushkin K;El-Kordi A;Ehrenreich H;Richter DW;Rusakov DA;Ponimaskin E
常见的神经递质5-羟色胺控制早期神经元分化的不同方面，尽管其潜在机制知之甚少。在这里，我们报告说，5-羟色胺5-HT 7受体的激活促进突触发生和增强突触活动在海马神经元在出生后的早期阶段。对Gα12缺陷小鼠的分析揭示了G12蛋白对神经元中5-HT 7受体介导的效应的关键作用。在幼年小鼠海马的器官型制备物中，5-HT 7 R/G12信号的刺激增强树突棘的形成，增加神经元的兴奋性，并调节突触可塑性。相反，在较老的神经元制剂中，5-HT 7/G12信号传导的形态发生和突触发生作用被消除。抑制5-HT 7受体对成年动物海马突触可塑性无影响。表达分析表明，5-HT 7和Gα12-蛋白在海马中的产生经历强烈的调节，在出生后的早期阶段有明显的短暂增加。因此，5-HT 7受体和Gα12蛋白的表达调节可能代表了5-羟色胺在出生后早期发育过程中特异性调节初始神经元网络形成的分子机制。
The common neurotransmitter serotonin controls different aspects of early neuronal differentiation, although the underlying mechanisms are poorly understood. Here we report that activation of the serotonin 5-HT7 receptor promotes synaptogenesis and enhances synaptic activity in hippocampal neurons at early postnatal stages. An analysis of Gα12-deficient mice reveals a critical role of G12-protein for 5-HT7 receptor-mediated effects in neurons. In organotypic preparations from the hippocampus of juvenile mice, stimulation of 5-HT7R/G12 signaling potentiates formation of dendritic spines, increases neuronal excitability, and modulates synaptic plasticity. In contrast, in older neuronal preparations, morphogenetic and synaptogenic effects of 5-HT7/G12 signaling are abolished. Moreover, inhibition of 5-HT7 receptor had no effect on synaptic plasticity in hippocampus of adult animals. Expression analysis reveals that the production of 5-HT7 and Gα12-proteins in the hippocampus undergoes strong regulation with a pronounced transient increase during early postnatal stages. Thus, regulated expression of 5-HT7 receptor and Gα12-protein may represent a molecular mechanism by which serotonin specifically modulates formation of initial neuronal networks during early postnatal development.