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

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 大脑的特点是高度的神经可塑性，其中回路水平的形成对 环境变化。越来越多的证据表明，大多数精神疾病都有一个发展过程， 这是这个复杂过程中早期扰动的结果。青春期是一个暴露在 改变环境照明是非常普遍的，因为50%的美国青少年报告说， 电脑、智能手机和平板电脑。这种人造光的强度和曝光时间 在人类历史上是前所未有的。尽管人们普遍暴露在夜间的光线中， 青少年，我们的大脑适应不规则环境照明的机制的知识， 仍然不完整。内侧杏仁核（MeA）在情绪处理中起着关键作用，也是情绪调节的重要机制之一。 区域等，其接收和处理光信息。因此，人工改变光照 水平、时间和规律可能会在这个区域产生混乱的信号，影响神经可塑性， 情绪反应。研究光是否影响MeA的神经可塑性，从而增加脆弱性 在青春期小鼠的焦虑和风险决策中，我开发了一种新的异常光协议， 模仿人类青少年暴露在阳光下。这个独立之路奖将提供机会， 我在神经生物学和行为神经科学方面的专业知识，同时发展我的纤维能力 光度法和RNA测序。目标1是建立在我们的初步数据表明，异常光暴露， 改变了青春期小鼠MeA中的神经递质可塑性，这种神经可塑性有助于它们的发育。 易受焦虑和危险行为的影响。在巴恩斯医生和杨医生的监督下，我将使用 爱荷华州赌博任务，以测试异常光照是否会改变青少年的冒险行为 成年老鼠在K99阶段，有了Ramanathan博士的额外指导，我将探索是否 使用基于纤维光度计的钙记录，异常光影响选定MeA神经元的神经活动， 行为老鼠在目标2中，在Preissl博士的监督下，我将研究异常光暴露是否 影响MeA神经元及其参与焦虑和风险选择行为的靶区域的基因表达， 如中央杏仁核和终纹床核。这些实验会让我做好准备 在R00阶段，我将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、纤维光度测定和平移小鼠 模型（目标3）。由于杏仁核是一个高度保守的结构，因此拟议的研究将是 与了解青春期发育期间改变环境照明的影响相关 以及设计适当的综合干预措施，以促进青少年的情感健康。

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.