Functional development of interneurons that mediate the vestibulo-ocular reflex

介导前庭眼反射的中间神经元的功能发育

• 批准号: 10300051
• 负责人: David Schoppik
• 金额: $ 59.77万
• 依托单位: NEW YORK UNIVERSITY SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-12-01 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10300051
• 关键词: Ablation; Acute; Adopted; Afferent Neurons; Anatomy; Behavior; Cell surface; Cells; Chronic; Cues; Data; Development; Disease; Electrophysiology (science); Equilibrium; Esthesia; Excision; Eye; Fishes; Functional disorder; Gene Expression Profile; Genetic; Goals; Hair Cells; Impaired health; Impairment; Interneurons; Knowledge; Lasers; Lateral; Ligands; Light; Link; Logic; Mediating; Mission; Modeling; Molecular; Motor Neurons; Mutation; Neurons; Optics; Pathology; Process; Property; Public Health; RNA; Reflex action; Research; Role; Sensory; Siblings; Source; Specific qualifier value; Specificity; System; Testing; Time; To specify; Transcript; United States National Institutes of Health; Work; Zebrafish; developmental disease; experimental study; in vivo; innovation; mutant; nerve supply; neural circuit; organ growth; receptor; sensor; single-cell RNA sequencing; tool; vestibular reflex; vestibulo-ocular reflex

Project Summary / Abstract The vestibular system is critical for maintaining balance reflexes, vital behaviors that are disturbed both in ag- ing and in several developmental disorders. While we know much about how the vestibular system functions we know considerably less about how it develops. To form functional circuits, neurons must adopt the correct identities and connect to appropriate partners. Many molecular mechanisms underlying these processes have been proposed but how these mechanisms work in the context of a specific system to generate behavior is not yet clear. We propose an innovative approach: to use the vestibulo-ocular reflex system of the larval zebrafish as a simple and tractable model to determine the origin of cues that specify vestibular interneuron identity. The vestibulo-ocular reflex circuit is a simple 3-neuron arc comprised of sensory neurons, interneurons, and motoneurons. Proper behavior requires that the right sensors (e.g. for upward tilts) be linked to the proper mo- toneurons (e.g. those that move the eyes down). Our lab has developed tools to determine interneuron identity anatomically and electrophysiologically. We can remove possible sources of identity cues (motoneurons and sensory neurons) either chronically, through genetic means, or acutely, through laser-mediated photoablation. Finally, we can collect and process neurons across development to profile their patterns of gene expression. This application proposes three Aims: To determine whether cues for interneuron identity arise from either (1) the motor neurons, (2) the sensory neurons, or (3) from local interactions between interneurons themselves. Completion of these experiments stands to make a significant contribution: to reveal the principles responsible for balance circuit development. As such, the work is a major step towards the long-term goal of using such an understanding to shed light on the mechanisms underlying vestibular and neurodevelopmental dysfunction.

项目摘要/摘要