Homeostatic Stabilization of Neural Function in Health and Disease

健康和疾病中神经功能的稳态稳定

• 批准号: 9152175
• 负责人: GRAEME W DAVIS
• 金额: $ 101万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-12-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9152175
• 关键词: Aging; Animals; Autistic Disorder; Biological Models; Brain; Brain Diseases; Calcium; Data; Disease; Disease model; Endoplasmic Reticulum; Epilepsy; Foundations; Genetic; Goals; Health; Immune signaling; Impairment; Learning; Life; Link; Memory; Modeling; Molecular; Nerve Degeneration; Nervous system structure; Neurological Models; Neurons; Neurophysiology - biologic function; Neurosciences; Peripheral Nervous System; Phosphotransferases; Property; Reproducibility; Role; Signal Pathway; Signal Transduction; Synapses; System; Theoretical model; Work; experimental study; insight; interest; nervous system disorder; neuroregulation; neurotransmission; neurotransmitter release; next generation; novel; presynaptic; relating to nervous system; sensor; theories

PROJECT SUMMARY/ABSTRACT The brain is astonishing in its complexity and capacity for change. It seems certain that the plasticity that drives our ability to learn and remember can only be meaningful in the context of otherwise stable, reproducible, and predictable baseline neural function. It is now clear that homeostatic signaling systems function throughout the central and peripheral nervous systems to stabilize neural function throughout life. As a consequence, it is widely believed that impaired or maladaptive homeostatic signaling will be directly relevant to the cause and progression of neurological diseases that include epilepsy, autism and neurodegeneration. However, despite widespread evidence for the homeostatic control of neural function throughout the animal kingdom and implicit relevance to disease and aging, very little is known about the underlying mechanisms. The field of homeostatic plasticity is wide open for exploration and the potential for transformative advancement in cellular and molecular neuroscience is tremendous. We are leading the rapidly emerging field of homeostatic plasticity, harnessing the power of unbiased model system genetics to identify and characterize fundamentally new cellular and molecular mechanisms of homeostatic signaling in the nervous system. Our experiments will define many of the first signaling pathways identified to participate in the homeostatic signaling systems that control presynaptic neurotransmitter release and intrinsic neural excitability. Our approaches have uncovered a novel activity of the innate immune signaling system, new trans-synaptic signaling pathways, novel calcium sensors, novel neuronal kinase signaling systems, new roles for the presynaptic endoplasmic reticulum and tangible links to neurological disease. As such, our data will provide a foundation for exploring the impact homeostatic plasticity in mammalian models of neurological disease including epilepsy, autism and neurodegeneration. Our data will also directly impact current theories and models of homeostatic signaling. Current theoretical models have captured widespread interest. Molecular insight will provide important new ideas and new constraints for the next generation of theoretical models of homeostatic plasticity, learning and memory.

项目总结/文摘