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顾者的认可和需求的沟通，这 需要评估感官信息，并做出适当和有意的动作。虽然这件事 这一过程被称为知觉运动发育，对于婴儿的社会纽带、认知发展、 和终身健康，神经元的基础在很大程度上仍然未知。这种严重的知识鸿沟源于 部分原因是操作新生儿大脑的困难，以及缺乏可靠的强健新生儿行为 传统实验动物的运动输出。为了解决这一缺陷，这项研究旨在揭示基本大脑 新生的小蝌蚪通过跳舞向父母乞讨食物，这是一种社交运动展示的机制。 我们将这一新的研究有机体和行为范式与先进的神经遗传学工具相结合 为婴儿交流询问知觉运动发育的神经基础。最近的数据来自 我们的实验室表明，父母的识别是基于嗅觉线索的，乞讨运动的显示是由 多巴胺信号转导，而脆性X蛋白FMRP在乞讨神经元中特异富含。在此基础上 稳健的初步数据，我们建议检验FMRP调节多巴胺能信号的假设 感觉运动发育所必需的。因为社会认可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识别和门活动 在活体成像和细胞消融实验中乞讨所需的多巴胺能神经元。我们 还将通过检测转录变化来测试FMRP在调节多巴胺能信号中的作用 FMRP基因敲除蝌蚪中的多巴胺敏感细胞与野生型动物的比较。最后，自愿性汽车 运动可能涉及纹状体神经元，初步表明乞讨的蝌蚪增加了纹状体 活动。我们将从功能上测试纹状体的多巴胺能输入在执行乞讨中的作用 并确定FMRP如何调节纹状体多巴胺信号。总而言之，拟议的实验将 系统剖析FMRP和多巴胺神经元调节婴儿社会认知的机制 并在研究有机体中进行交流，具有实验可控性和强大的社会动力输出， 在其他研究生物体中很难实现。作为分子因素和整体脑组织 社会运动行为在脊椎动物中是保守的，这项研究将确定可概括的原则 知觉运动发育，这是一种对婴儿生存和终身健康至关重要的行为。