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 生物体适应环境条件的季节性变化以生存。这些改编依赖 主要在光周期（即日长）上，但也受温度的影响。最近的研究表明 光周期变化会影响昼夜节律涉及的大脑区域的神经元组成（即每天） 计时和调节多巴胺能神经元的数量，在称为神经递质的过程中 交换。其他研究表明，大脑在整个季节都会发生深刻的结构变化。 但是，这些功能和结构变化之间的关系与季节性适应 仍然是知识的主要差距。此外，是否其他相关的季节性提示，特别是温度， 对这些变化的贡献尚不清楚。该项目的总体目标是了解性质和角色 神经元可塑性在季节性提示的整合中，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 以及响应环境线索的氨基电路。为了测试这一点，我提出了3个具体目标：调查 （1）昼夜节律神经元网络的结构和功能可塑性以及（2）AMINEGIC电路 对季节性提示及其对社交和运动行为的影响，（3）确定塑料的影响 昼夜节律的变化和AMINEGIC电路调节大脑连接性并编码行为 这些电路的输出。我将在遗传上可处理的果蝇模型中完成这个项目，并将 利用多功能神经遗传学，高分辨率显微镜和良好行为的组合 分析。 到目前为止，在我在加州大学戴维斯分校的Chiu实验室的博士后职业中，我获得了分子遗传学的培训 和生物化学，我用来探索昼夜节律在调节季节性适应中的作用 果蝇。向前迈进，我将基于目前的研究来研究季节性的神经元机制 可塑性和行为。在K99培训期间，我将使用果蝇中的可用工具来评估 昼夜节律神经元和氨基电路的功能和结构变化，以响应季节性 提示。此外，我将通过使用可用的遗传编码来测试这些更改的功能后果 传感器并通过生成新的，更敏感的传感器来评估体内的AMINEGIC功能 Lin Tian博士。我将在R00阶段扩展这些工具的使用，以确定如何相互作用 这两个电路系统调节其功能以及它们如何共同影响季节性行为。我相信 博士的指导。 Chiu和Tian以及K​​99/R00奖提供的支持，将允许 我要建立一个强大的基础，这将使我成为独立调查员的成功。结果 拟议的研究将在季节性的背景下阐明神经元基础的感觉积分 适应，阐明了健康生理和疾病的季节性调节背后的机制。