Photoperiodic Programming of Serotonin Neurons

血清素神经元的光周期编程

• 批准号: 10399697
• 负责人: DOUGLAS G MCMAHON
• 金额: $ 6.68万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2022-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10399697
• 关键词: Acute; Affective; Anxiety; Behavior; Behavioral; Biological Clocks; Bipolar Disorder; Brain; Brain region; Cell Nucleus; Cells; Development; Disease; Dorsal; Electrophysiology (science); Experimental Models; Fluorescent in Situ Hybridization; Gene Activation; Gene Expression Profiling; Gene Expression Regulation; Genes; Glutamates; Health; Human; In Situ Hybridization; Knockout Mice; Laboratories; Life; Light; Lighting; Major Depressive Disorder; Mediating; Mental Depression; Midbrain structure; Modeling; Molecular; Mood Disorders; Mus; Neonatal; Neuraxis; Neurons; Neurophysiology - biologic function; Neurosciences; Norepinephrine; Phenotype; Photoperiod; Play; Psyche structure; RNA; Reverse Transcriptase Polymerase Chain Reaction; Rodent; Role; Seasonal Affective Disorder; Serotonin; Signal Transduction; Synapses; Testing; Visual system structure; anxiety-like behavior; circadian; circadian pacemaker; critical period; dorsal raphe nucleus; electrical property; experimental study; fetal; multi-electrode arrays; neural circuit; neurobehavioral disorder; neurobiological mechanism; neurochemistry; neuromechanism; neurotransmission; noradrenergic; novel; photoperiodicity; postnatal development; prenatal; programs; relating to nervous system; transcription factor; transcriptome; transcriptome sequencing

PROJECT SUMMARY A fundamental question in neuroscience is how environmental signals may have long-lasting effects on neural circuits and neural function. The circadian clock and circadian photoperiod are associated with mood disorders, but the neurobiological mechanisms are unknown. Dysregulation of serotonin neurotransmission is implicated in neurobehavioral disorders, such as depression and anxiety, and alterations in the serotonergic phenotype of raphe neurons has dramatic effects on affective behaviors in rodents. The serotonergic dorsal raphe nuclei receive light input from the circadian visual system, as well as polysynaptic input from the biological clock nuclei, and dorsal raphe serotonin neurons respond acutely to tonic illumination with increased spike rate and to changes in the circadian light cycle with gene activation. Our laboratory has demonstrated that seasonal circadian photoperiods (winter –like “short days” vs. summer-like “long days”) can induce enduring changes in mouse dorsal raphe serotonin neurons - programming their spontaneous neural activity, and altering depression and anxiety-like behaviors. Here we seek to elucidate the mechanistic basis photoperiodic programming of serotonin neurons, focusing on electrophysiology, gene regulation and maternal-fetal vs neonatal developmental windows. We will examine neural mechanisms of photoperiodic programming of dorsal raphe serotonin neurons using both multi-electrode array and whole cell electrophysiology; altered gene regulation in serotonin neurons induced by photoperiodic programming using RT-PCR, RNA-seq gene expression analysis of FACS sorted serotonin neurons and RNA Scope in situ hybridization to determine the photoperiod programming transcriptome, and the gene network in serotonergic neurons driven by photoperiodic programming. We will test the hypothesis that the Pet-1 transcription factor is a critical node for photoperiodic programing and define critical periods for the enduring effects of photoperiod. Successful completion of these aims will reveal novel mechanisms by which a pervasive environmental signal – the daily light cycle – can influence the long-term function of brain serotonergic neurons and the behaviors they mediate.

项目摘要 神经科学中的一个基本问题是环境信号如何对神经系统产生长期影响。 电路和神经功能。生物钟和昼夜光周期与情绪障碍有关， 但神经生物学机制尚不清楚。5-羟色胺神经传递失调与 在神经行为障碍，如抑郁症和焦虑症，以及神经元能表型的改变， 中缝核神经元对啮齿类动物的情感行为有显著影响。中缝背核的肾上腺素能 接收来自昼夜视觉系统的光输入，以及来自生物钟的多突触输入 核和中缝背核5-羟色胺神经元对强直性照明的反应是急性的， 与基因激活引起的昼夜光周期变化有关。我们的实验室已经证明， 昼夜光周期（冬季的“短日”与夏季的“长日”）可以诱导植物生长的持久变化。 小鼠中缝背核5-羟色胺神经元-编程它们的自发神经活动， 抑郁症和类似焦虑的行为。在这里，我们试图阐明光周期的机制基础 5-羟色胺神经元的编程，重点是电生理学，基因调控和母胎vs 新生儿发育窗我们将研究光周期编程的神经机制， 背中缝5-羟色胺神经元使用多电极阵列和全细胞电生理学;改变 RT-PCR、RNA-seq研究光周期编程诱导5-羟色胺神经元的基因调控 流式细胞仪分选的5-羟色胺神经元的基因表达分析和RNA Scope原位杂交，以确定 光周期编程转录组，和基因网络在多巴胺能神经元驱动的 光周期编程我们将测试Pet-1转录因子是一个关键节点的假设， 光周期规划和定义光周期的持久影响的关键时期。成功 这些目标的完成将揭示一种新的机制，通过这种机制，一种普遍存在的环境信号--日常的 光周期-可以影响脑内多巴胺能神经元的长期功能和它们的行为， 调解。