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

基本信息

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
项目类别：
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

项目摘要

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.

项目概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且有意的动作。虽然这过程，称为知觉运动发展，对于婴儿的社会联系、认知发展、和终生健康，神经元基础仍然很大程度上未知。这种严重的知识差距源于部分原因在于操纵新生儿大脑的困难以及缺乏可靠的强有力的新生儿行为传统实验动物的运动输出。为了解决这一缺陷，这项研究旨在揭示大脑的基本功能新生儿社交运动展示的机制是利用社交蝌蚪通过跳舞向父母乞求食物。我们将这种新颖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询问婴儿交流知觉运动发育的神经元基础。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，乞讨运动的显示是由多巴胺信号传导，而脆弱的 X 蛋白 FMRP 在乞讨神经元中特别丰富。基于此可靠的初步数据，我们建议检验 FMRP 调节多巴胺能信号传导的假设知觉运动发育所需的。由于社会认可是婴儿交流的重要组成部分对于护理人员，我们将确定嗅觉线索如何编码护理人员的识别并控制其活动使用体内成像和细胞消融实验展示乞讨所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与野生型动物相比，FMRP 敲除蝌蚪中的多巴胺敏感细胞。最后，自愿运动运动可能涉及纹状体神经元，初步表明乞讨蝌蚪增加了纹状体神经元的数量。活动。我们将对纹状体的多巴胺能输入在执行乞讨中的作用进行功能测试行为并确定 FMRP 如何调节纹状体多巴胺信号传导。总之，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和具有实验易处理性和强大的社会运动输出的研究有机体中的交流在其他研究生物体中很难实现。由于分子因素和整体大脑组织社会运动行为在脊椎动物中是保守的，这项研究将确定社会运动行为的普遍原则知觉运动发育，这是一种对婴儿生存和终生福祉至关重要的行为。