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.

概括 青春期是大脑和行为发展的脆弱性和机会的时期。皮质 多巴胺系统轴突的脊柱修剪和产物是青春期大脑的两个标志 可以在人类，灵长类动物和啮齿动物中观察到的发展（Delevich等，2021）。探索，风险 从出生地点或家族群体散布是青少年的核心行为里程碑 在许多物种中的发展，但我们目前不了解这些行为如何以及为什么受到调节 通过神经生物学的变化（Lin＆Wilbrecht，2022）。这些主题之间的关系对 研究是因为青少年发展计划可能会因实验室动物的驯化而破坏。 野生物种的小鼠spicilegus提出了一个令人兴奋的模型，其中研究青少年 开发和冒险服用是因为它根据出生的季节显示出不同的生活历史轨迹。 M. Spicilegus在春季和夏季出生于漫长的日子（LD）在生命的头三个月中分散，而M。 Spicilegus出生于较短的秋季（SD）延迟在冬季延迟散布。我们正在繁殖这些 在实验室环境下的小鼠比较将表达青少年发育的年龄匹配的小鼠 在不同时间表上的程序。在初步数据中，我们确认，当我们在 SD 10H：14H灯：深色光周期，它们显示体重增加减少并减少了新颖的物体研究 与12h：12h饲养的小鼠相比（Cryns等，2022）。 在这里，我们将测试光周期的差异改变风险。 Spicilegus通过影响纹状体尾巴的发育（TS）。我们决定专注于 由于最近的工作表明TS中的多巴胺释放在TS调节和撤退 在新物体的背景下的行为（Menegas等，2018； Akiti等，2022）。这使它令人兴奋 控制大胆的青少年探索行为的较大曲目的候选人支持纳塔尔 分散。在AIM 1中，我们将在离体切片中使用新建立的Nircat成像（Beyene等，2019）和 纤维光度法在Dlight的体内记录，以测试短日（SD）和漫长的一天（LD）的饲养方式 光周期会影响纹状体尾部的多巴胺释放。在AIM 2中，我们将测试如何简短饲养 天（SD）和漫长的一天（LD）光周期会影响脊柱修剪的皮质神经元，这些神经元将投射到尾巴上的皮质神经元 纹状体。 光周期操纵将产生新的对比度，使我们能够将年龄与功能分离。 这些数据将具有影响力，因为它们将有助于隔离发展以调节的机制 青少年冒险和相关行为。这些数据可能会对 了解人类青春期的脆弱性和机会。