Investigating the role of sleep in synaptic reorganization after neural injury

研究睡眠在神经损伤后突触重组中的作用

• 批准号: 10530705
• 负责人: Jeffrey Michael Donlea
• 金额: $ 39万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-12-01 至 2026-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10530705
• 关键词: Acute; Adult; Astrocytes; Axon; Axotomy; Back; Biological Assay; Brain; Cell membrane; Data; Development; Drosophila genus; Drosophila melanogaster; Endocytosis; Excision; Gene Expression; Genes; Genetic; Injury; Intervention; Libraries; Mediating; Membrane; Microglia; Modeling; Molecular; Mushroom Bodies; Mutation; Nerve; Nerve Degeneration; Neurites; Neuroglia; Neuronal Injury; Neuronal Plasticity; Neurons; Neuropeptides; Neurophysiology - biologic function; Neurotransmitters; Olfactory Receptor Neurons; Peptide Receptor; Peptides; Phagocytes; Phagocytosis; Process; Proteins; Public Health; Recovery; Regulator Genes; Role; Signal Transduction; Sleep; Sleep Deprivation; Sleep disturbances; Sleeplessness; Synapses; Synaptic plasticity; Tachykinin; Testing; Trauma; Wallerian Degeneration; axon injury; axonal degeneration; cell type; confocal imaging; experimental study; fly; genetic regulatory protein; injured; insight; memory encoding; mutant; nerve injury; nerve transection; neural; neurochemistry; neuromechanism; neuroprotection; presynaptic; prevent; programs; receptor; response; response to injury; sleep regulation; synaptic pruning; synthetic enzyme

Project Summary Sleep has been identified as a state of heightened neural plasticity, but the rules that govern reorganization during sleep remain unknown. To better identify the conditions under which synapses are pruned during sleep, we have begun to examine responses to neural injury in the fruit fly. After antennal transection, flies acutely increase their sleep for up to one day before returning back to baseline levels. Our preliminary data also show that pre-synaptic active zones are removed more rapidly than plasma membrane after antennal injury, and that sleep deprivation after injury prevents the clearance of pre-synapses from injured olfactory receptor neurons. In this project, we will examine: (1) signals that are generated after injuries to promote sleep; (2) contributions of glial cell types to sleep regulation and synapse removal after injury; and (3) molecular mechanisms that promote synapse removal during sleep. We anticipate that these experiments will provide insight into the role for sleep in response to neural trauma, and begin to investigate the consequences of disrupted sleep on recovery from axotomy.

项目摘要 睡眠被认为是一种神经可塑性增强的状态，但支配重组的规则 在睡眠中仍然未知。为了更好地识别睡眠期间突触被修剪的条件， 我们已经开始研究果蝇对神经损伤的反应。触角切断后， 在恢复到基线水平之前，增加他们的睡眠时间长达一天。我们的初步数据还显示 在触角损伤后，突触前活性区比质膜更快地被去除， 损伤后的睡眠剥夺阻止了突触前体从损伤的嗅觉受体神经元的清除。 在这个项目中，我们将研究：（1）受伤后产生的信号，以促进睡眠;（2）贡献 神经胶质细胞类型对睡眠调节和损伤后突触去除的影响;以及（3） 促进睡眠时突触的移除。我们预计，这些实验将提供深入了解的作用， 并开始研究睡眠中断对神经损伤的影响。 从轴突损伤中恢复过来