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.

项目总结 焦虑和危险行为是青少年面临的最普遍的心理健康问题。青春期 大脑的特点是具有高度的神经可塑性，其中电路层的形成对 环境变化。越来越多的证据表明，大多数精神障碍都有发育性 这是这一复杂过程中早期扰动的结果。青春期是一段暴露在 改变环境光线无疑是很常见的，据报道，美国50%的青少年使用 睡前使用电脑、智能手机和平板电脑。这种人造光的强度和曝光时间 过去的日落在人类历史上是前所未有的。尽管人们普遍暴露在夜间的灯光下 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。杏仁内侧核(Mea)在情绪处理中起着关键作用，也是 其中包括接收和处理光信息的区域。因此，人工改变光曝光量 水平、时间和规律性可能会在这个区域产生混乱的信号，影响神经可塑性和 情绪反应。研究光照是否影响大脑中动脉的神经可塑性，从而增加其易损性。 对于青春期小鼠的焦虑和风险决策，我开发了一种新的异常光方案，旨在 模拟人类青春期的光线暴露。这个独立之路奖将提供一个机会 在发展我的纤维能力的同时，建立我在神经生物学和行为神经科学方面的专业知识 光度和RNA测序。目标1是建立在我们的初步数据基础上的，这些数据表明反常的光暴露 改变青春期小鼠MEA中的神经递质可塑性，并且这种神经可塑性有助于其 易受焦虑和危险行为的影响。在巴恩斯博士和杨博士的监督下，我将使用 爱荷华州赌博任务测试异常光线暴露是否会以不同方式改变青少年的冒险行为 和成年小鼠。在K99阶段Ramanathan博士的额外指导下，我将探索 用纤维光度法钙离子记录研究异常光对所选MEA神经元的神经活动的影响 行为不端的老鼠。在目标2中，在Preissl博士的监督下，我将调查异常光线暴露 影响MeA神经元及其参与焦虑和危险选择行为的靶区的基因表达， 如杏仁中央核和终纹床核。这些实验将使我做好准备 在R00阶段，我将通过以下方式研究杏仁核回路在光介导的焦虑和危险行为中的作用 结合杏仁核神经元的药理学操作、纤维光度法和翻译小鼠 模型(目标3)。由于杏仁核是一个保存完好的结构，因此拟议的研究将是 与理解青春期发育期间改变的环境照明的影响有关的翻译 并设计适当的综合干预措施，以促进青少年的情绪健康。