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Activity-dependent regulation of Sonic hedgehog signaling incortical astrocytes

声波刺猬信号传导皮质星形胶质细胞的活动依赖性调节

基本信息

批准号：
10320950
负责人：
Anna Denise Resurreccion Garcia
金额：
$ 22.73万
依托单位：
DREXEL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2021
资助国家：
美国
起止时间：
2021-01-01 至 2023-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10320950
关键词：
Adult Apical Astrocytes Attenuated Brain Cells Communication Complex Data Dendrites Dendritic Spines Elements Embryo Environment Exhibits Exposure to Foundations Gene Deletion Gene Expression Genetic Goals Housing Impairment Mediating Modality Molecular Motor Cortex Mus Mutant Strains Mice Nervous system structure Neuroglia Neurons Neurosciences Phenotype Physical activity Physiological Population Property Regulation Reporter Role SHH gene Shapes Signal Pathway Signal Transduction Social Interaction Somatosensory Cortex Source Stimulus Supporting Cell Synapses Synaptic plasticity Time Transcriptional Activation Vertebral column Visual Cortex cell type density environmental enrichment for laboratory animals experience inward rectifier potassium channel neurodevelopment neuronal excitability novel postnatal postnatal development programs recruit relating to nervous system response smoothened signaling pathway transcription factor

项目摘要

PROJECT ABSTRACT Understanding the mechanisms by which the CNS adapts to novel experiences and changing environments is a fundamental goal of neuroscience. Following experience and neural activity, neurons undergo changes in gene expression and synaptic organization that facilitate such adaptation. Though historically regarded as simple support cells for neurons, astrocytes are gaining increasing recognition as essential elements of the synapse, modulating synaptic connectivity and function. This suggests that reciprocal interactions between neurons and astrocytes are likely to be involved in experience-dependent synaptic plasticity. The molecular mechanisms underlying neuronal interactions with astrocytes during experience-dependent activity are not well understood. In previous studies, we identified astrocytes as the predominant cell type transducing Sonic hedgehog (Shh) signaling derived from neurons in the postnatal and adult cortex. Selective disruption of Shh activity in astrocytes impairs structural and functional properties of cortical neurons, demonstrating that Shh signaling is required for the proper establishment of developing circuits. In this study, we propose to examine the role of activity in regulating Shh signaling. We will use an enriched environment with complex stimuli that include novelty, increased physical activity and social interactions, to investigate the role of experience in stimulating Shh. In Aim 1, we will identify the stimuli that promote experience-dependent Shh activity and determine whether it is modality-specific. In Aim 2, we will use genetic marking strategies and chemogenetic approaches to identify the cells that initiate experience-dependent Shh signaling and determine whether neuronal activity stimulates Shh activity. These data will lay the foundation for further mechanistic studies aimed at elucidating the molecular programs initiated by activity-dependent neuron-astrocyte communication mediated by Shh signaling.

项目摘要