Integration of seasonal cues to modulate neuronal plasticity

整合季节性线索来调节神经元可塑性

基本信息

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
项目类别：
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

项目摘要

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.

项目概要生物体适应环境条件的季节变化才能生存。这些调整依赖于主要受光周期（即日长）影响，但也受温度影响。最近的研究表明光周期变化影响涉及昼夜节律（即每天）的大脑区域的神经元组成在称为神经递质的过程中计时并调节多巴胺能神经元的数量交换。其他研究表明，大脑也会随着季节的变化而发生深刻的结构变化。然而，大脑的这些功能和结构变化与季节适应之间的关系仍然是知识上的重大差距。此外，其他相关的季节性线索，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作用神经元可塑性在整合季节性线索以促进季节性适应中的作用。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响应环境线索的胺能电路。为了测试这一点，我提出了 3 个具体目标：调查 (1) 生物钟神经元网络和 (2) 胺能回路的结构和功能可塑性对季节性线索的反应及其对社交和运动行为的影响，以及（3）确定塑料如何生物钟和胺能回路的变化调节大脑连接并编码行为这些电路的输出。我将在遗传易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、高分辨率显微镜和成熟的行为学的组合分析。到目前为止，在加州大学戴维斯分校 Chiu 实验室的博士后生涯中，我接受了分子遗传学方面的培训和生物化学，我用它来探索昼夜节律肽在调节季节适应中的作用果蝇。展望未来，我将在目前的研究基础上研究季节性的神经元机制可塑性和行为。在K99训练期间，我将使用Drosophila中可用的工具来评估生物钟神经元和胺能回路响应季节的功能和结构变化提示。此外，我将通过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生成新的、更灵敏的传感器来评估体内胺能功能林田博士。我将在R00阶段扩展这些工具的使用，以确定它们之间如何交互这两个回路系统调节它们的功能以及它们如何协调地影响季节性行为。我相信博士的指导。 Chiu 和 Tian 加上 K99/R00 奖项提供的支持，将使我要打下坚实的基础，使我能够作为一名独立调查员取得成功。结果拟议的研究将阐明季节性背景下感觉统合的神经元基础适应，揭示健康生理和疾病的季节性调节背后的机制。