Developmental Origins of Affective Disorders

5-羟色胺(5-羟色胺)既是一种神经递质，也是一种生长因子，调节大脑功能和 大脑发育。此外，5-羟色胺与多种疾病的病因和治疗有关 神经精神障碍。具体地说，针对5-羟色胺系统的药物，如选择性5-羟色胺 重摄取抑制剂(SSRI)目前被用作治疗抑郁症和焦虑症的一线药物 精神错乱。此外，有几条证据表明，常见的 5-羟色胺转运体基因(5HTT)启动子区域的多态与 易患神经精神障碍，如神经质、抑郁和焦虑。其他人和我们 曾假设这些变体在大脑早期对成年人的情绪行为产生影响 发展。 我们以前已经证明，这种遗传倾向可以在小鼠身上通过结构性5HTT来建模。 消融。此外，我们还证明了发育性5-HTT阻断(PNFLX治疗) 模拟了遗传性5HTT消融的效果，支持了5-HTT发育中断的假设 功能会引起成人情绪行为的变化。然而，关于5-羟色胺如何作用于大脑的知识 发育，特别是与成人焦虑和抑郁相关的行为，仍然受到以下因素的阻碍 知识上的多重鸿沟。 我们提出的实验旨在填补这些空白，并专注于研究早期5-HTT的影响 封锁了中缝功能的发展。第一个目标是研究中缝的生理学 PNFLX处理的小鼠的5-羟色胺能神经元。第二个目标将研究电路介导的调制 对PNFLX治疗小鼠的中缝生理学的影响。第三个目标是研究5-羟色胺的解剖学。 在PNFLX处理的小鼠中的系统。最后，我们的第四个目标将调查中缝活动的因果关系。 在抑郁症和焦虑症的病因学方面。

Serotonin (5-HT) functions both as a neurotransmitter and as a growth factor to modulate brain function and brain development. In addition, 5-HT has been implicated in the etiology and treatment of numerous neuropsychiatric disorders. Specifically, drugs which target the 5-HT system, such as selective 5-HT reuptake inhibitors (SSRIs) are currently used as the first-line treatment for depression and anxiety disorders. Furthermore, several lines of evidence suggest that commonly occurring functional polymorphisms in the promoter region of the serotonin transporter gene (5htt) are associated with increased susceptibility to neuropsychiatric disorders such as neuroticism, depression, and anxiety. Others and we have hypothesized that these variants exert their effects on adult emotional behavior during early brain development. We have preiviously shown that this genetic predisposition can be modeled in mice by constitutive 5htt ablation. Furthermore, we have demonstrated that developmental 5-HTT blockade (PNFLX treatment) mimics the effect of genetic 5htt ablation, supporting the hypothesis that developmental disruption of 5-HTT function elicits changes in adult emotional behavior. Yet, knowledge of how serotonin acts to alter brain development, especially as it relates to adult anxiety and depression-related behaviors, is still hampered by multiple gaps in knowledge. Our proposed experiments aim at filling these gaps and focus on investigating the effects of early-life 5-HTT blockade on the development of raphe function. The first aim vyill investigate the physiology of raphe serotonergic neurons in PNFLX treated mice. The second aim will investigate circuitry mediated modulation of raphe physiology in PNFLX treated mice. The third aim will investigate the anatomy of the serotonin system in PNFLX treated mice. Finally, our fourth aim will investigate the causal involvement of raphe activity in the etiology of depression and anxiety-like behaviors.