Integration of seasonal cues to modulate neuronal plasticity

项目摘要 生物要适应季节变化的环境条件才能生存。这些适应依赖于 主要是光周期(即日长)，但也受温度的影响。最近的研究表明 光周期变化影响与昼夜节律有关的大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 正在切换。其他研究表明，大脑也会在不同季节经历深刻的结构变化。 然而，大脑的这些功能和结构变化与季节性适应之间的关系 仍然是知识方面的一个主要差距。此外，其他相关的季节性迹象，特别是温度， 导致这些变化的原因尚不清楚。本项目的总体目标是了解其性质和作用 神经元在整合季节性线索以促进季节性适应方面的可塑性。我的假设是 季节性适应是由来自昼夜节律的神经元的功能和结构可塑性调节的 以及对环境提示作出反应的胺能回路。为了检验这一点，我提出了三个具体目标：调查 脑内(1)生物钟神经元网络和(2)胺能回路的结构和功能可塑性 对季节性提示的反应及其对社交和运动行为的影响，以及(3)决定塑料如何 生物钟和胺能回路的变化调节大脑的连通性并编码行为 这些电路的输出。我将在基因易驯化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相结合 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多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，研究季节性疾病的神经机制。 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 昼夜节律时钟神经元和胺能回路的功能和结构变化对季节的响应 暗示。此外，我将通过使用可用的遗传编码来测试这些变化的功能后果 并通过产生新的、更灵敏的传感器来评估体内的胺能功能 林田博士的名字。我将在R00阶段扩展这些工具的使用，以确定 这两个回路系统协调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，加上K99/R00奖提供的支持，将允许 我需要建立一个强大的基础，使我能够成为一名成功的独立调查员。评选结果 拟议的研究将在季节性的背景下阐明感觉整合的神经元基础 适应，揭示了健康生理和疾病的季节性调节背后的机制。

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.