Integration of seasonal cues to modulate neuronal plasticity

整合季节性线索来调节神经元可塑性

• 批准号: 10723977
• 负责人: Sergio Ignacio Hidalgo Sotelo
• 金额: $ 10.57万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-07-01 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10723977
• 关键词: Affect; Animal Model; Animals; Area; Autopsy; Award; Behavior; Behavioral; Binding; Biochemistry; Biogenic Amines; Biology; Brain; Calendar; Cells; Cues; Disease; Dopamine; Drosophila genus; Etiology; Exhibits; Exposure to; Fluorescent in Situ Hybridization; Foundations; Generations; Goals; Health; Hour; Human; Hypothalamic structure; Immunohistochemistry; Knowledge; Light; Link; Mammals; Mediating; Membrane; Mental Depression; Mentors; Mentorship; Methods; Microscopy; Modeling; Molecular Genetics; Motor Activity; Nature; Neuronal Plasticity; Neurons; Neuropeptides; Neurotransmitters; Organism; Outcome; Output; Peptides; Periplasmic Binding Proteins; Photoperiod; Physiology; Positioning Attribute; Postdoctoral Fellow; Prevalence; Process; Proteins; Reporting; Research; Research Personnel; Resolution; Role; Seasonal Affective Disorder; Seasonal Variations; Seasons; Serotonin; Signal Transduction; Structure; Synapses; System; Temperature; Testing; Therapeutic; Time; Training; Variant; career; circadian; circadian pacemaker; day length; density; dopaminergic neuron; dynamic system; fly; functional plasticity; human disease; in vivo; insight; light intensity; neurogenetics; neuronal circuitry; paraventricular nucleus; photoperiodicity; response; sensor; sensory integration; social; success; suprachiasmatic nucleus; tool; transcriptomics

Project Summary Organisms adapt to seasonal changes in environmental conditions to survive. These adaptations rely predominantly on photoperiod (i.e., daylength), but are also influenced by temperature. Recent studies indicate that photoperiodic changes affect the neuronal composition of brain areas involved in circadian (i.e., daily) timekeeping and modulate the number of dopaminergic neurons, in a process known as neurotransmitter switching. Other studies show that the brain also undergoes profound structural changes across seasons. However, the relationship between these functional and structural changes in the brain and seasonal adaptations remains a major gap in knowledge. Moreover, whether other relevant seasonal cues, in particular temperature, contribute to these changes is not known. The overall goal of this project is to understand the nature and role of neuronal plasticity in the integration of seasonal cues to promote seasonal adaptations. My hypothesis is that seasonal adaptations are mediated by functional and structural plasticity in neurons from circadian and aminergic circuits in response to environmental cues. To test this, I propose 3 specific aims: investigate structural and functional plasticity of (1) the circadian clock neuronal network and of (2) aminergic circuits in response to seasonal cues and its impact on social and locomotor behavior, and (3) determine how the plastic changes in the circadian clock and aminergic circuits regulate brain connectivity and encode the behavioral output of these circuits. I will accomplish this project in the genetically tractable Drosophila model and will leverage a combination of versatile neurogenetics, high-resolution microscopy, and well-established behavioral analysis. Thus far in my postdoctoral career in the Chiu lab at UC Davis, I obtained training in molecular genetics and biochemistry, which I used to explore the role of circadian peptides in modulating seasonal adaptations in Drosophila. Moving forward, I will build on my current research to study the neuronal mechanisms of seasonal plasticity and behavior. During the K99 training period, I will use available tools in Drosophila to assess the functional and structural changes in the circadian clock neurons and aminergic circuits in response to seasonal cues. Moreover, I will test the functional consequences of these changes by using available genetically encoded sensors and by generating new, more sensitive, sensors to assess aminergic function in vivo under the guidance of Dr. Lin Tian. I will expand the use of these tools in the R00 stage to determine how the interaction between these two circuit systems modulate their functions and how they affect seasonal behavior concertedly. I believe that the mentorship of Drs. Chiu and Tian, together with the support provided by the K99/R00 award, will allow me to build a strong foundation that will enable my success as an independent investigator. The results of the proposed studies will elucidate the neuronal basis underlying sensory integrations in the context of seasonal adaptations, shedding light on the mechanisms behind seasonal modulation of health physiology and disorders.

项目摘要 生物适应环境条件的季节性变化以生存。这些适应依赖于 主要依赖于光周期（即，日照长度），但也受到温度的影响。最近的研究表明 光周期变化影响昼夜节律中涉及的脑区域的神经元组成（即，每日） 计时和调节多巴胺能神经元的数量，这一过程被称为神经递质 切换其他研究表明，大脑在不同季节也会发生深刻的结构变化。 然而，大脑中这些功能和结构变化与季节适应之间的关系 仍然是一个重大的知识缺口。此外，是否其他相关的季节线索，特别是温度， 对这些变化的贡献是未知的。本项目的总体目标是了解 神经元可塑性在整合季节性线索，以促进季节性适应。我的假设是 季节性适应是由昼夜节律神经元的功能和结构可塑性介导的， 和胺能回路对环境线索的反应。为了验证这一点，我提出了三个具体目标：调查 结构和功能可塑性（1）昼夜节律钟神经元网络和（2）胺能电路， 对季节性线索的反应及其对社会和运动行为的影响，以及（3）确定塑料如何 生物钟和胺能回路的变化调节大脑的连通性， 这些电路的输出。我将在遗传学上易于处理的果蝇模型中完成这个项目， 利用多功能神经遗传学、高分辨率显微镜和成熟的行为学的组合， 分析. 到目前为止，在我的博士后生涯中，在加州大学戴维斯分校的邱实验室，我获得了分子遗传学的培训 和生物化学，我用它来探索昼夜节律肽在调节季节性适应中的作用， 果蝇展望未来，我将在我目前的研究基础上，研究季节性神经元机制。 可塑性和行为。在K99培训期间，我将使用果蝇中可用的工具来评估 昼夜节律钟神经元和胺能回路在季节性变化中的功能和结构变化 线索此外，我将使用可用的基因编码来测试这些变化的功能后果。 传感器，并通过产生新的，更敏感的传感器，以评估在指导下，在体内胺能功能 林天博士我将在R 00阶段扩展这些工具的使用，以确定 这两个回路系统协调地调节它们的功能以及它们如何影响季节性行为。我相信 赵博士和田博士的指导，以及K99/R 00奖提供的支持，将使 我希望我能建立一个坚实的基础，使我能够成功地成为一名独立的调查员。的结果 拟议的研究将阐明在季节性环境中感觉整合的神经基础， 适应，揭示了健康生理和疾病的季节性调节背后的机制。