Effects of light exposure on amygdala plasticity during adolescence: implications for anxiety and well-being

青春期光照对杏仁核可塑性的影响：对焦虑和幸福感的影响

• 批准号: 10604589
• 负责人: Alessandra Porcu
• 金额: $ 24.89万
• 依托单位: UNIVERSITY OF SOUTH CAROLINA AT COLUMBIA
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-11-09 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10604589
• 关键词: Adolescence; Adolescent; Adult; Affect; Amygdaloid structure; Anatomy; Anxiety; Anxiety Disorders; Award; Behavior; Behavioral; Biological Assay; Brain; Brain region; Calcium; Calcium Signaling; Cells; Cellular Phone; Choice Behavior; Chronic; Complex; Computers; Coupled; Data; Decision Making; Development; Electronics; Emotional; Emotional disorder; Emotions; Exposure to; Feeling suicidal; Fiber; Gambling; Gene Expression; Gene Expression Profile; Genes; Health; Human; Hypothalamic structure; Immunohistochemistry; Impairment; In Situ Hybridization; Individual; Intervention; Iowa; Knowledge; Label; Lead; Light; Lighting; Link; Medial; Mediating; Mental Health; Mental disorders; Mentorship; Modernization; Mood Disorders; Moods; Mus; Neurobiology; Neuronal Plasticity; Neurons; Neurosciences; Neurotransmitters; Output; Pathway interactions; Pattern; Personal Satisfaction; Pharmacology; Phase; Photometry; Play; Population; Positioning Attribute; Predisposition; Process; Property; Protocols documentation; RNA; Recording of previous events; Reporting; Research; Risk; Risk Behaviors; Risk Factors; Risk-Taking; Rodent; Role; Signal Transduction; Societies; Somatostatin; Structure; Structure of terminal stria nuclei of preoptic region; Supervision; Synapses; Tablets; Testing; Time; Well in self; Youth; anxiety-like behavior; base; behavior test; critical period; design; emotional behavior; environmental change; experimental study; gamma-Aminobutyric Acid; in vivo; light effects; mouse model; neural circuit; relating to nervous system; response; screening; single-cell RNA sequencing; transcriptome sequencing

PROJECT SUMMARY Anxiety and risky behaviors are the most prevalent mental health concerns facing adolescents. The adolescent brain is characterized by a high degree of neural plasticity in which circuit-level formation is very responsive to environmental changes. There is increasing evidence that most psychiatric disorders have a developmental origin that is the result of early disturbances in this complex process. Adolescence is a period in which exposure to altered environmental lighting is decidedly common, as 50% of adolescents in the USA reported using computers, smartphones, and tablets before bedtime. This intensity of artificial light and the duration of exposure past sunset is unprecedented in human history. Despite the widespread exposure to night-time light in adolescents, our knowledge of the mechanisms by which our brain adapts to irregular environmental lighting is still incomplete. The medial amygdala (MeA) plays a key role in processing emotions and is also one of the regions, among others, that receives and processes light information. Thus, artificial changes in light exposure levels, timing, and regularity might generate confusing signals in this region, affecting neuroplasticity and emotional responses. To study whether light affects neuroplasticity in the MeA, thereby increasing vulnerability to anxiety and risk-decision making in adolescent mice, I developed a new aberrant light protocol designed to mimic human adolescent light exposure. This Pathway to Independence Award will provide the opportunity to build on my expertise in neurobiology and behavioral neuroscience while developing my abilities in fiber photometry and RNA-sequencing. Aim 1 is built upon our preliminary data showing that aberrant light exposure alters neurotransmitter plasticity in the MeA of adolescent mice, and that such neuroplasticity contributes to their vulnerability to anxiety and risky behaviors. Under the supervision of Dr. Barnes and Dr. Young, I will use the Iowa Gambling Task to test whether aberrant light exposure alters risk-taking behaviors differently in adolescent and adult mice. With additional mentorship from Dr. Ramanathan in the K99 phase, I will explore whether aberrant light affects neural activity in selected MeA neurons using fiber photometry-based calcium recording in behaving mice. In Aim 2, under the supervision of Dr. Preissl, I will investigate whether aberrant light exposure affects gene expression in MeA neurons and its target regions participating in anxiety and risky choice behaviors, such as the central amygdala and the bed nucleus of the stria terminalis. These experiments will prepare me for the R00 phase in which I will study the role of amygdala circuitry in light-mediated anxiety and risky behavior by combining pharmacological manipulation of amygdalar neurons, fiber photometry, and translational mouse models (Aim 3). Because the amygdala is a well-conserved structure, the proposed research will be translationally relevant for understanding the effect of altered environmental lighting during pubertal development and for the design of appropriate integrative interventions to promote emotional well-being in adolescents.

项目摘要 焦虑和危险行为是青少年面临的最普遍的心理健康问题。青少年 大脑的特征是高度的神经可塑性，其中电路级的形成对 环境变化。越来越多的证据表明大多数精神疾病都有发展 起源是这种复杂过程中早期干扰的结果。青春期是暴露的时期 对于改变环境照明的改变绝对是常见的，因为美国有50％的青少年报告使用 就寝前的计算机，智能手机和平板电脑。这种人造光的强度和暴露时间 过去的日落在人类历史上是前所未有的。尽管广泛暴露于夜间光线 青少年，我们对大脑适应不规则环境照明的机制的了解是 仍然不完整。内侧杏仁核（MEA）在处理情绪中起关键作用，也是 除其他区域，这些区域将接收和处理光明信息。因此，人工变化光暴露 水平，时机和规律性可能会在该区域产生混乱的信号，从而影响神经可塑性和 情绪反应。研究光线是否影响MEA中的神经可塑性，从而增加脆弱性 对于青少年小鼠的焦虑和风险决策，我开发了一种新的异常光协议 模仿人类青少年的光暴露。这项获得独立奖的途径将为 建立在神经生物学和行为神经科学方面的专业知识的基础上，同时发展我的纤维能力 光度法和RNA序列。 AIM 1建立在我们的初步数据上，表明异常暴露 改变青少年小鼠MEA中神经递质的可塑性，这种神经可塑性有助于其 焦虑和冒险行为的脆弱性。在Barnes博士和Young博士的监督下，我将使用 爱荷华州的赌博任务以测试异常的光暴露在青少年中是否改变了冒险行为 和成年小鼠。在Ramanathan博士在K99阶段的额外指导下，我将探讨是否探讨是否是否 异常光使用基于纤维光度法的钙记录在选定的MEA神经元中的神经活动 行为小鼠。在AIM 2中，在Preissl博士的监督下，我将调查是否异常暴露 影响MEA神经元及其目标区域的基因表达，参与焦虑和冒险选择行为， 例如中央杏仁核和质末端的床核。这些实验会为我做好准备 我将研究杏仁核电路在光介导的焦虑和风险行为中的作用的R00阶段 结合杏仁核神经元，纤维光度法和翻译小鼠的药理操作 模型（目标3）。由于杏仁核是一种保存良好的结构，因此拟议的研究将是 对于理解青春期开发过程中环境照明改变的效果的翻译相关 以及设计适当的综合干预措施，以促进青少年的情感健康。