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认可护理人员和需求的交流，这 需要评估感官信息并进行适当和有意的运动。虽然这个 过程，称为感知运动的发展，对于婴儿的社会联系，认知发展至关重要， 和终生的福祉，神经元基础在很大程度上未知。知识的严重差距是 一部分，从操纵新生儿大脑的困难和坚固的新生儿行为不足 传统实验室动物的运动输出。为了解决这一赤字，这项研究旨在发现基本的大脑 使用社会t的新生社会运动机制展示了通过跳舞来乞求父母吃食物的机制。 我们将这种新颖的研究生物和行为范式与先进的神经遗传学工具结合在一起 询问婴儿交流感知运动发育的神经元基质。最新数据来自 我们的实验室表明，父母的识别是基于嗅觉提示，乞讨电动机显示由 多巴胺信号传导和脆弱的X蛋白FMRP专门在乞讨神经元中富集。基于此 强大的初步数据，我们建议测试FMRP调节多巴胺能信号传导的假设 感知运动发展所需的。因为社会认可是婴儿交流的关键组成部分 对于看护人，我们将确定嗅觉提示如何编码护理人员的识别和门的活动 使用体内成像和细胞消融实验乞讨显示的多巴胺能神经元。我们 还将测试FMRP通过检查转录变化的转录变化来调整多巴胺能信号传导的作用 与野生型动物相比，FMRP基因敲除t中的多巴胺敏感细胞。最后，自愿发动机 运动可能涉及纹状体神经元，初步表明乞讨t的纹状体增加 活动。我们将在执行乞讨中的功能上测试多巴胺能输入到纹状体中的作用 行为并确定FMRP如何调音纹状体多巴胺信号传导。一起，提出的实验将 系统地剖析FMRP和多巴胺神经元调节婴儿社会认可的机制 以及具有实验性障碍性和强大的社交运动输出的研究生物体中的交流 在其他研究生物中很难实现。作为分子因素和整体大脑组织 社会运动行为在整个脊椎动物之间是保存的，这项研究将确定可概括的原则 感知运动的发展，这是婴儿生存和终身福祉至关重要的行为。