Serotonin acts through its receptors (5-HTRs) to shape brain networks during development and modulates essential functions in mature brain. The 5-HT_1AR is mainly located at soma of hippocampal neurons early during brain development and its expression gradually shifts to dendrites during postnatal development. The 5-HT₇R expressed early during hippocampus development, shows a progressive reduction in its expression postnatally. Considering these changes during development, we evaluated in cultured hippocampal neurons whether the 5-HT_1AR and 5-HT₇R change their expression, modulate dendritic growth, and activate signaling pathways such as ERK1/2, AKT/GSK3β and LIMK/cofilin, which may sustain dendrite outgrowth by controlling cytoskeleton dynamics.

We show that mRNA levels of both receptors increase between 2 and 7 DIV; however only protein levels of 5-HT₇R increase significantly at 7 DIV. The 5-HT_1AR is preferentially distributed in the soma, while 5-HT₇R displays a somato-dendritic localization at 7 DIV. Through stimulation with 5-HT at 7 DIV during 24 h and using specific antagonists, we determined that 5-HT_1AR decreases the number of primary and secondary dendrites and restricts the growth of primary dendrites. The activation of 5-HT_1AR and 5-HT₇R promotes the growth of short secondary dendrites and triggers ERK1/2 and AKT phosphorylation through MEK and PI3K activation respectively; without changes in the phosphorylation of LIMK and cofilin. We conclude that 5-HT_1AR restricts dendritogenesis and outgrowth of primary dendrites, but that both 5-HT_1AR and 5-HT₇R promote secondary dendrite outgrowth. These data support the role of 5-HT in neuronal outgrowth during development and provide insight into cellular basis of neurodevelopmental disorders.

5-羟色胺通过其受体（5-HTR）起作用，在发育过程中塑造大脑网络，并调节成熟大脑的基本功能。5-HT _1A R主要位于大脑发育早期的海马神经元体中，其表达在产后发育过程中逐渐移向树突。在海马体发育早期表达的5-HT ₇ R，显示出其出生后表达的逐渐减少。考虑到发育过程中的这些变化，我们在培养的海马神经元中评估了5-HT _1A R和5-HT ₇R改变它们的表达，调节树突状生长，并激活诸如ERK1 / 2，AKT /GSK3β和LIMK / cofilin的信号通路，这些通路可能通过控制细胞骨架动力学来维持树突生长。

我们表明两种受体的mRNA水平在2到7 DIV之间增加；然而，在7 DIV时，只有5-HT ₇ R的蛋白质水平显着增加。5-HT _1A R优先分布在体中，而5-HT ₇ R在7 DIV处显示体树突状定位。通过在24小时内于7 DIV用5-HT刺激并使用特异性拮抗剂，我们确定5-HT _1A R减少了初级和次级树突的数量并限制了初级树突的生长。5-HT _1A R和5-HT ₇的活化R促进短次级树突的生长，并分别通过MEK和PI3K激活触发ERK1 / 2和AKT磷酸化；没有改变LIMK和cofilin的磷酸化。我们得出结论，5-HT _1A R限制了树突的生成和初级树突的生长，但是5-HT _1A R和5-HT ₇ R都促进了次生树突的生长。这些数据支持了5-HT在发育过程中神经元增生中的作用，并为神经发育障碍的细胞基础提供了见识。