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

基本信息

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
项目类别：
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

项目摘要

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.

项目概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。青少年时期大脑的特点是具有高度的神经可塑性，其中电路级的形成非常敏感环境变化。越来越多的证据表明，大多数精神疾病都与发育有关起源是这个复杂过程中早期干扰的结果。青春期是一个暴露的时期改变环境照明显然是很常见的，因为 50% 的美国青少年报告使用睡前使用电脑、智能手机和平板电脑。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。尽管人们普遍暴露在夜间光线下对于青少年来说，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）在处理情绪方面发挥着关键作用，也是大脑的重要组成部分之一。其中，接收和处理光信息的区域。因此，人为改变光照水平、时间和规律性可能会在该区域产生令人困惑的信号，影响神经可塑性和情绪反应。研究光是否影响 MeA 的神经可塑性，从而增加脆弱性针对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，旨在模仿人类青少年时期的光照。该独立之路奖将提供机会建立我在神经生物学和行为神经科学方面的专业知识，同时发展我在纤维方面的能力光度测定和 RNA 测序。目标 1 是建立在我们的初步数据之上的，该数据显示异常的光照改变青春期小鼠 MeA 中的神经递质可塑性，并且这种神经可塑性有助于其容易产生焦虑和危险行为。在 Barnes 博士和 Young 博士的监督下，我将使用爱荷华州赌博任务测试异常光照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，在 Ramanathan 博士的额外指导下，我将探讨是否使用基于光纤光度测定的钙记录，异常光会影响选定 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，我将调查是否有异常的曝光影响 MeA 神经元及其参与焦虑和危险选择行为的目标区域的基因表达，例如杏仁核中央和终纹床核。这些实验将使我做好准备在 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、纤维光度测定法和转化小鼠模型（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环境照明改变的影响具有转化相关性以及设计适当的综合干预措施以促进青少年的情绪健康。