Sonic Hedgehog Dependent Neuron-Astrocyte Crosstalk During Cortical Circuit Assembly

皮质电路组装过程中声波刺猬依赖性神经元-星形胶质细胞串扰

• 批准号: 10307403
• 负责人: COREY C HARWELL
• 金额: $ 40.32万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2028-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10307403
• 关键词: Ablation; Astrocytes; Behavior; Biological Assay; Brain; Brothers; Cell Adhesion Molecules; Cell Nucleus; Cell physiology; Cerebral cortex; Chemical Synapse; Communication; Complement; Complex; Data; Development; Electrical Synapse; Electron Microscopy; Electrophysiology (science); GLI Family Protein; Gene Expression; Genes; Genetic; Genetic Transcription; Histology; Homeostasis; Human; Intellectual functioning disability; Ions; Maintenance; Mediating; Molecular; Nature; Nervous System; Neurodevelopmental Disorder; Neuroglia; Neurons; Neurophysiology - biologic function; Pathway interactions; Performance; Play; Process; Proteins; Publishing; Regulation; Role; SHH gene; Signal Pathway; Signal Transduction; Specific qualifier value; Specificity; Synapses; Testing; Therapeutic Intervention; Work; autism spectrum disorder; cell behavior; cell type; cytokine; experimental study; insight; light microscopy; loss of function; mouse genetics; mutant; neural circuit; neurotransmitter reuptake; programs; receptor; response; synaptic function; synaptogenesis; therapeutic development; tool

Project Summary Neuronal-glial relationships play a critical role in the regulation of synapse formation and neuronal specification. The cellular and molecular mechanisms by which neurons and astrocytes communicate and coordinate are not well understood. The experiments in this proposal will uncover the molecular and cellular mechanisms by which neuron derived SHH protein can coordinate the cell behaviors of cortical astrocytes to facilitate the formation and function of neural circuits in the brain. In our studies we take advantage of the large complement of mouse genetic tools that allows us to specifically manipulate Shh signaling in astrocytes. Using cutting edge light and electron microscopy approaches we will define how specific interactions between astrocytes and neurons are dependent on Shh signaling and assess how astrocytes influence the development of functional circuits. Collectively these aims will provide a framework for understanding the delivery, reception and cellular response to SHH in the developing cortex.

项目总结