Department of Genetics, Harvard Medical School, Boston, MA, USA.
Department of Anesthesiology, Perioperative and Pain Medicine Research, Children's Hospital Boston, Boston, MA, USA.
Nat Rev Neurosci. 2019 Jul;20(7):397-424. doi: 10.1038/s41583-019-0151-3.
Neurons that synthesize and release 5-hydroxytryptamine (5-HT; serotonin) express a core set of genes that establish and maintain this neurotransmitter phenotype and distinguish these neurons from other brain cells. Beyond a shared 5-HTergic phenotype, these neurons display divergent cellular properties in relation to anatomy, morphology, hodology, electrophysiology and gene expression, including differential expression of molecules supporting co-transmission of additional neurotransmitters. This diversity suggests that functionally heterogeneous subtypes of 5-HT neurons exist, but linking subsets of these neurons to particular functions has been technically challenging. We discuss recent data from molecular genetic, genomic and functional methods that, when coupled with classical findings, yield a reframing of the 5-HT neuronal system as a conglomeration of diverse subsystems with potential to inspire novel, more targeted therapies for clinically distinct 5-HT-related disorders.
合成并释放 5-羟色胺（5-HT；血清素）的神经元表达一组核心基因，这些基因确立并维持这种神经递质表型，并将这些神经元与其他脑细胞区分开来。除了共同的 5-HT 能表型外，这些神经元在解剖学、形态学、发生学、电生理学和基因表达方面表现出不同的细胞特性，包括支持额外神经递质共传递的分子的差异表达。这种多样性表明存在功能异质的 5-HT 神经元亚型，但将这些神经元的亚群与特定功能联系起来在技术上具有挑战性。我们讨论了来自分子遗传学、基因组学和功能方法的最新数据，这些数据与经典发现相结合，重新定义了 5-HT 神经元系统为具有不同潜在功能的多种子系统的集合，这可能为临床上不同的 5-HT 相关疾病提供新的、更有针对性的治疗方法。
