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:
- 金额:$ 24.89万
- 依托单位:
- 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:
- 关键词:AdolescenceAdolescentAdultAffectAmygdaloid structureAnatomyAnxietyAnxiety DisordersAwardBehaviorBehavioralBiological AssayBrainBrain regionCalciumCalcium SignalingCellsCellular PhoneChoice BehaviorChronicComplexComputersCoupledDataDecision MakingDevelopmentElectronicsEmotionalEmotional disorderEmotionsExposure toFeeling suicidalFiberGamblingGene ExpressionGene Expression ProfileGenesHealthHumanHypothalamic structureImmunohistochemistryImpairmentIn Situ HybridizationIndividualInterventionIowaKnowledgeLabelLeadLightLightingLinkMedialMediatingMental HealthMental disordersMentorshipModernizationMood DisordersMoodsMusNeurobiologyNeuronal PlasticityNeuronsNeurosciencesNeurotransmittersOutputPathway interactionsPatternPersonal SatisfactionPharmacologyPhasePhotometryPlayPopulationPositioning AttributePredispositionProcessPropertyProtocols documentationRNARecording of previous eventsReportingResearchRiskRisk BehaviorsRisk FactorsRisk-TakingRodentRoleSignal TransductionSocietiesSomatostatinStructureStructure of terminal stria nuclei of preoptic regionSupervisionSynapsesTabletsTestingTimeWell in selfYouthanxiety-like behaviorbasebehavior testcritical perioddesignemotional behaviorenvironmental changeexperimental studygamma-Aminobutyric Acidin vivolight effectsmouse modelneural circuitrelating to nervous systemresponsescreeningsingle-cell RNA sequencingtranscriptome 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。
项目成果
期刊论文数量(0)
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{{ truncateString('Alessandra Porcu', 18)}}的其他基金
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:
10294253 - 财政年份:2020
- 资助金额:
$ 24.89万 - 项目类别:
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:
10705220 - 财政年份:2020
- 资助金额:
$ 24.89万 - 项目类别:
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