The role of Protocadherin-17 in the development of direction selective circuits in the zebrafish visual system

Protocadherin-17 在斑马鱼视觉系统方向选择电路发育中的作用

基本信息

批准号：
10582919
负责人：
JAMES DAVID JONTES
金额：
$ 43.31万
依托单位：
OHIO STATE 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：
2023-09-30 至 2025-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10582919
关键词：
Action Potentials Adhesions Affect Amygdaloid structure Axon Bacterial Artificial Chromosomes Behavior Brain Calcium Cell Adhesion Molecules Child Data Defect Dendrites Dendritic Spines Development Disease Dorsal Elements Environment Epilepsy Exhibits Family Fertilization Ganglia Goals Growth Human Image Impairment In Vitro Intellectual functioning disability Larva Learning Link Measures Mediating Midbrain structure Molecular Mood Disorders Morphology Muscle fasciculation Mutation Nervous System Neural Pathways Neurons Neuropil Pattern Photons Photoreceptors Play Process Proteins Retina Retinal Ganglion Cells Role Schizophrenia Stimulus Structure Synapses Synaptic plasticity System Tectum Mesencephali Testing Time Translating Vision Visual Visual System Work Zebrafish autism spectrum disorder axon growth cell growth density developmental disease differential expression experience in vivo in vivo imaging insight member migration mutant nerve stem cell neural neural circuit neurodevelopment novel response superior colliculus Corpora quadrigemina synaptogenesis temporal measurement transgene expression two-photon vision development visual processing visual stimulus

Action Potentials Adhesions Affect Amygdaloid structure Axon Bacterial Artificial Chromosomes Behavior Brain Calcium Cell Adhesion Molecules Child Data Defect Dendrites Dendritic Spines Development Disease Dorsal Elements Environment Epilepsy Exhibits Family Fertilization Ganglia Goals Growth Human Image Impairment In Vitro Intellectual functioning disability Larva Learning Link Measures Mediating Midbrain structure Molecular Mood Disorders Morphology Muscle fasciculation Mutation Nervous System Neural Pathways Neurons Neuropil Pattern Photons Photoreceptors Play Process Proteins Retina Retinal Ganglion Cells Role Schizophrenia Stimulus Structure Synapses Synaptic plasticity System Tectum Mesencephali Testing Time Translating Vision Visual Visual System Work Zebrafish autism spectrum disorder axon growth cell growth density developmental disease differential expression experience in vivo in vivo imaging insight member migration mutant nerve stem cell neural neural circuit neurodevelopment novel response superior colliculus Corpora quadrigemina synaptogenesis temporal measurement transgene expression two-photon vision development visual processing visual stimulus

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项目摘要

ABSTRACT During development, neural progenitors divide to produce nascent neurons, which migrate and extend axons and dendrites. These neurons form synapses with their neighbors and begin to assemble functional circuits, which mature as synaptic connectivity is refined and additional neurons are integrated into these circuits. Defects in these assembly processes can result in a broad range of problems, including visual processing disorders. Protocadherin-17 (Pcdh17) is a homophilic cell adhesion molecule that is important for collective outgrowth of amygdala axons and to mediate contact-dependent axon growth in vitro, as well as short-term synaptic plasticity. Our preliminary data show circuit-level defects in the optic tectum of the larval zebrafish, with a decrease in the proportion of direction selective neurons and an increase of non-selective neurons. We also provide data showing that neurons of the optic tectum can fasciculate and co-arborize during circuit formation. We hypothesize that loss of Pcdh17 adhesion results in altered patterns of arbor growth and synaptogenesis, which degrades the selectivity of neuronal responses. In this developmental/exploratory R21, we will examine: 1) the developmental trajectory of visual responses in pcdh17 mutants to better define when and how these responses diverge from wild type larva, and 2) the developmental trajectories of axonal and dendritic arbor growth and synaptogenesis in wild type and mutant larvae. These results could reveal a novel cellular mechanism for the assembly of local circuitry and provide insight into how cellular growth processes govern the maturation of neural responses.

抽象的在发育过程中，神经祖细胞分裂以产生新生的神经元，迁移和延伸轴突和树突。这些神经元与邻居形成突触，并开始组装功能充满成熟作为突触连通性的电路被完善，并将其他神经元整合到这些中电路。这些组装过程中的缺陷可能导致广泛的问题，包括视觉处理障碍。原钙粘着蛋白17（PCDH17）是一种同质细胞粘附分子，对杏仁核轴突的集体产物生长，并介导体外接触依赖性轴突生长以及短期突触可塑性。我们的初步数据显示了幼虫的视觉层中电路级缺陷斑马鱼，方向选择性神经元的比例降低，非选择性的增加神经元。我们还提供了数据，显示视神经膜的神经元可以着迷并共同化在电路形成期间。我们假设PCDH17粘附的损失导致植物的模式改变生长和突触发生，它降低了神经元反应的选择性。在这个发展/探索性R21，我们将研究：1）视觉反应的发展轨迹 PCDH17突变体可以更好地定义这些反应与野生型幼虫的不同，以及2）轴突和树突状乔木生长以及野生型和突变体突触发生的发育轨迹幼虫。这些结果可能揭示了一种新型的细胞机制，用于组装局部电路并提供深入了解细胞生长过程如何控制神经反应的成熟。