Dopamine regulation of infant perceptual motor development and communication

多巴胺对婴儿知觉运动发育和交流的调节

• 批准号: 10735199
• 负责人: Lauren A O'Connell
• 金额: $ 58.08万
• 依托单位: STANFORD UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-01 至 2028-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735199
• 关键词: Ablation; Address; Afferent Neurons; Animals; Behavior; Behavioral; Behavioral Paradigm; Brain; Brain region; Caregivers; Cells; Child; Communication; Corpus striatum structure; Cues; Cyclic GMP; Dancing; Data; Development; Disease; Dopamine; Drug Targeting; Exhibits; FMR1; FMRP; Food; Foundations; Fragile X Syndrome; Gene Expression Profile; Genes; Genetic; Genetic Transcription; Goals; Human; Imaging Device; Infant; Infant Development; Knock-out; Knowledge; Laboratory Animals; Lead; Learning; Mammals; Measures; Molecular; Mothers; Motor; Motor Skills; Motor output; Movement; Nervous System; Neurons; Nucleus Accumbens; Olfactory Learning; Olfactory Pathways; Organism; Parents; Perception; Personal Satisfaction; Process; Proteins; Recovery; Regulation; Research; Role; Sensory; Signal Pathway; Signal Transduction; Social Development; Social Environment; Synapses; Tadpoles; Testing; Vertebrates; Visual; Visualization; Work; autistic children; cell type; cognitive development; dopaminergic neuron; experimental study; follow-up; in vivo imaging; insight; knockout animal; motor behavior; motor disorder; neonate; neural; neural circuit; neurogenetics; novel; pup; response; social; social attachment; social organization; stem; tool

Project Summary Healthy development in children relies on social recognition of caregivers and communication of needs, which requires evaluating sensory information and making appropriate and intentional movements. Although this process, referred to as perceptual motor development, is critical for infant social bonding, cognitive development, and lifelong wellbeing, the neuronal basis remains largely unknown. This severe gap in knowledge stems, in part, from the difficulty in manipulating neonate brains and a paucity of robust neonate behaviors as reliable motor outputs in traditional laboratory animals. To address this deficit, this research aims to uncover basic brain mechanisms of neonate social-motor displays using social tadpoles that beg their parents for food by dancing. We combine this novel research organism and behavioral paradigm with advanced neurogenetic tools to interrogate the neuronal substrates of perceptual motor development for infant communication. Recent data from our lab shows that parental recognition is based on olfactory cues, the begging motor display is regulated by dopamine signaling, and the fragile X protein FMRP is enriched specifically in begging neurons. Based on this robust preliminary data, we propose to test the hypothesis that FMRP regulates the dopaminergic signaling required for perceptual motor development. As social recognition is a critical component of infant communication towards caregivers, we will determine how olfactory cues encode caregiver recognition and gate the activity of dopaminergic neurons necessary for begging displays using in vivo imaging and cell ablation experiments. We will also test the role of FMRP in tuning dopaminergic signaling by examining transcriptional changes in dopamine-sensitive cells in FMRP knockout tadpoles compared to wild type animals. Finally, voluntary motor movements likely involve striatal neurons and preliminary suggests begging tadpoles have increased striatal activity. We will functionally test the role of the dopaminergic inputs into the striatum in executing begging behavior and determine how FMRP tunes striatal dopamine signaling. Together, the proposed experiments will systematically dissect the mechanisms by which FMRP and dopamine neurons regulate infant social recognition and communication in a research organism with experimental tractability and a robust social-motor output that is difficult to achieve in other research organisms. As the molecular factors and overall brain organization of social-motor behaviors are conserved across vertebrates, this research will identify generalizable principles of perceptual motor development, a behavior critical for infant survival and life-long wellbeing.

项目摘要 儿童的健康发展依赖于社会对照料者的认可和需要的交流， 需要评估感官信息并做出适当且有意识的动作。虽然这 这个过程，被称为知觉运动发展，对于婴儿的社会联系、认知发展， 和终身幸福，神经元的基础在很大程度上仍然未知。这种严重的知识差距源于， 部分原因是由于难以操纵新生儿的大脑和缺乏可靠的新生儿行为， 传统实验室动物的运动输出。为了解决这一问题，这项研究旨在揭示基本的大脑 新生儿的社会运动显示机制使用社会蝌蚪，乞求他们的父母通过跳舞的食物。 我们将联合收割机这种新的研究生物体和行为范例与先进的神经遗传学工具相结合， 询问婴儿沟通知觉运动发育的神经元基质。最近的数据 我们的实验室表明，父母的识别是基于嗅觉线索，乞讨运动的显示是由 多巴胺信号传导，脆性X蛋白FMRP在乞讨神经元中特异性富集。基于此 强大的初步数据，我们建议测试的假设，FMRP调节多巴胺能信号 感知运动发展所必需的。由于社会认知是婴儿沟通的重要组成部分 对于照顾者，我们将确定嗅觉线索如何编码照顾者的识别和门的活动， 使用体内成像和细胞消融实验显示乞讨所必需的多巴胺能神经元。我们 还将通过检查转录变化来测试FMRP在调节多巴胺能信号传导中的作用， 多巴胺敏感细胞在FMRP敲除蝌蚪相比，野生型动物。最后，自愿运动 运动可能涉及纹状体神经元，初步研究表明，乞讨蝌蚪的纹状体神经元数量增加， 活动我们将在功能上测试多巴胺能输入纹状体在执行乞讨中的作用 行为和确定FMRP如何调谐纹状体多巴胺信号。总之，拟议的实验将 系统地剖析了FMRP和多巴胺神经元调节婴儿社会识别的机制 在一个具有实验性易处理性和强大的社会运动输出的研究有机体中进行交流， 这在其他研究生物体中是很难实现的。作为分子因素和整体大脑组织的 社会运动行为在脊椎动物中是保守的，这项研究将确定 知觉运动发育，一种对婴儿生存和终身幸福至关重要的行为。