Photoperiodic Programming of Serotonin Neurons

血清素神经元的光周期编程

基本信息

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
项目类别：
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

项目摘要

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.

项目摘要神经科学的一个基本问题是环境信号如何对神经科学产生长期影响电路和神经功能。昼夜节律和昼夜节律光周期与情绪障碍有关，但是神经生物学机制尚不清楚。 5-羟色胺神经传递的失调涉及在神经行为疾病中，例如抑郁和动画，以及血清素能表型的改变强奸神经元对啮齿动物的情感行为具有巨大影响。血清素能背raphe核从昼夜节目的视觉系统中接收光输入，以及生物时钟的多突触输入细胞核和背侧raphe 5-羟色胺神经元对补品照明的反应，峰值速率增加和用基因激活改变昼夜节律的光周期。我们的实验室已经证明了那个季节昼夜节律光周期（冬季 - 像夏季一样的“漫长的日子”）可能会导致持久的变化鼠标背侧raphe 5-羟色胺神经元 - 编程其赞助神经元，并改变抑郁和类似焦虑的行为。在这里，我们试图阐明机械基础光周期 5-羟色胺神经元的编程，重点是电生理学，基因调节和母亲 - 宠儿与新生儿发展窗户。我们将检查光周期编程的神经机制使用多电极阵列和全细胞电生理学的背侧raphe 5-羟色胺神经元；改变使用RT-PCR，RNA-SEQ诱导的5-羟色胺神经元中的基因调节 FACS的基因表达分析分类的血清素神经元和RNA范围原位杂交确定光周期编程转录组和串联神经元中的基因网络由光周期编程。我们将检验以下假设：PET-1转录因子是关键节点光周期编程并定义了光周期持久影响的关键时期。成功的这些目标的完成将揭示出普遍环境信号的新型机制 - 每日光周期 - 可以影响脑血清能神经元的长期功能及其行为调解。