Tail of the striatum and regulation of exploratory behavior in a wild mouse

野生小鼠纹状体尾部和探索行为的调节

• 批准号: 10753855
• 负责人: Linda E Wilbrecht
• 金额: $ 24.08万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10753855
• 关键词: ARHGEF5 gene; Adolescence; Adolescent; Adolescent Behavior; Adolescent Development; Adolescent Risk Behavior; Age; Animals; Apical; Area; Axon; Behavior; Behavioral; Body Weight decreased; Brain; Brain region; Breeding; C57BL/6 Mouse; Corpus striatum structure; Darkness; Data; Detection; Development; Dissociation; Dopamine; Elements; Ethology; Exploratory Behavior; Fiber; Goals; Human; Image; Injections; Investigation; Label; Laboratories; Learning; Life; Light; Measures; Modeling; Motivation; Mus; Nest Leaving; Neurobiology; Neurons; Nucleus Accumbens; Photometry; Photoperiod; Primates; Regulation; Rewards; Risk Taking; Rodent; Seasons; Siblings; Site; Slice; Tail; Technology; Testing; Time; Vertebral column; Virus; Weight Gain; Work; adolescent brain development; density; dopamine system; in vivo; life history; nanosensors; neural; novel; programs; psychologic; season of birth; timeline; tool

Summary Adolescence is a time of both vulnerability and opportunity for brain and behavioral development. Cortical spine pruning and outgrowth of the axons of the dopamine system are two hallmarks of adolescent brain development that can be observed in humans, primates, and rodents (Delevich et al. 2021). Exploration, risk taking, and dispersal from the natal site or familial group are core behavioral milestones of adolescent development in many species, yet we currently do not understand how and why these behaviors are regulated by changes in neurobiology (Lin & Wilbrecht, 2022). The relationship between these topics is challenging to study because programs for adolescent development are likely disrupted by domestication in lab animals. A wild species of mouse, Mus spicilegus, presents an exciting model in which to study adolescent development and risk taking because it shows different life history trajectory depending on season of birth. M. spicilegus born in spring and summer on long days (LD) disperse in the first three months of life, while M. spicilegus born on shorter autumnal days (SD) delay dispersal through the wintertime. We are breeding these mice in a laboratory context to compare age-matched mice who will express adolescent developmental programs on different timelines. In preliminary data we confirmed that when we reared M. spicilegus on an SD 10h:14h light:dark photoperiod, they showed reduced weight gain and reduced novel object investigation compared to 12h:12h reared mice (Cryns et al., 2022). Here we will test the idea that differences in photoperiod alter risk taking exploratory behavior in M. spicilegus via effects on the development of the tail of the striatum (TS). We have decided to focus on the TS area because of recent work showing that dopamine release in the TS regulates approach and retreat behavior in the context of a novel object (Menegas et al., 2018; Akiti et al., 2022). This makes it an exciting candidate for the control of a larger repertoire of bold adolescent exploratory behaviors that support natal dispersal. In Aim 1, we will use newly established nIRCat imaging in ex vivo slices (Beyene et al., 2019) and fiber photometry in vivo recording of dLight to test how rearing in short day (SD) and long day (LD) photoperiod impacts dopamine release in the tail of the striatum. In Aim 2, we will test how rearing in short day (SD) and long day (LD) photoperiod impacts spine pruning on the cortical neurons that project to the tail of the striatum. Photoperiod manipulation will create new contrasts that allow us to dissociate age from function. These data will be impactful because they will help to isolate mechanisms that evolved to regulate adolescent risk-taking and dispersal related behavior. These data can have broad impact on understanding vulnerabilities and opportunities in human adolescence.

总结 青春期是大脑和行为发育的脆弱期和机会期。皮质 脊椎修剪和多巴胺系统轴突的生长是青少年大脑的两个标志 可在人类、灵长类动物和啮齿类动物中观察到的发育（Delevich等人，2021）。探索，风险 从纳塔尔地或家庭群体中带走和驱散是青少年的核心行为里程碑 在许多物种的发展，但我们目前还不知道如何以及为什么这些行为是受管制的 神经生物学的变化（Lin & Wilbrecht，2022）。这些主题之间的关系具有挑战性， 因为青少年发展的计划可能会被实验室动物的驯化所破坏。 一种野生小鼠，Mus spicilegus，为研究青少年提供了一个令人兴奋的模型。 发展和风险承担，因为它显示了不同的生活史轨迹取决于出生季节。M. 长日春、夏季出生的刺足螨在出生后3个月内就开始消散; 在较短的秋日（SD）出生的spicilegus延迟了整个冬季的扩散。我们正在培育这些 小鼠在实验室环境中比较年龄匹配的小鼠谁将表达青春期发育 不同时间线上的节目在初步数据中，我们证实，当我们饲养M。安氏针茅 SD 10 h：14 h光：暗光周期，它们表现出体重增加减少和新目标调查减少 与12小时：12小时饲养的小鼠相比（Cryns等，2022年）。 在这里，我们将测试的想法，不同的光周期改变冒险探索行为的M。 通过影响纹状体尾部（TS）的发育来治疗spicilegus。我们决定把重点放在 TS区域，因为最近研究表明TS中的多巴胺释放调节接近和撤退 在新对象的上下文中的行为（Menegas等人，2018; Akiti等人，2022年）。这使它成为一个令人兴奋的 候选人的控制更大的剧目大胆的青少年探索行为，支持纳塔尔 分散在目标1中，我们将在离体切片中使用新建立的nIRCat成像（Beyene等人，2019年）和 纤维光度法在体记录dLight，以测试短日（SD）和长日（LD）饲养 光周期影响纹状体尾部的多巴胺释放。在目标2中，我们将测试如何饲养， 白天（SD）和长日照（LD）光周期影响投射到尾部的皮层神经元上的脊柱修剪 纹状体。 光周期操纵将创造新的对比，使我们能够将年龄与功能分离开来。 这些数据将是有影响力的，因为它们将有助于隔离进化到调节的机制。 青少年冒险和分散相关行为。这些数据可能会产生广泛的影响 了解人类青春期的脆弱性和机会。