权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Experience-dependent Cellular Plasticity Mechanisms

经验依赖的细胞可塑性机制

基本信息

批准号：
10540335
负责人：
HOLLIS T. CLINE
金额：
$ 68.37万
依托单位：
SCRIPPS RESEARCH INSTITUTE, THE
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 2025-12-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10540335
关键词：
Address Amblyopia Animals Behavior Behavioral Behavioral Assay Biological Assay Brain Brain Injuries Cell physiology Date of birth Development Electrophysiology (science)Event Functional Imaging Goals Image Impairment Injury Investigation Knowledge Label Mass Spectrum Analysis Metabolic Modeling Molecular Molecular Genetics Nerve Degeneration Nervous System Neuronal Plasticity Neurons Optics Photic Stimulation Protein Biosynthesis Protein Dynamics Protein Synthesis Induction Proteins Proteomics Protocols documentation RNA Transport RNA-Binding Protein FUS RNA-Binding Proteins Recovery Rehabilitation therapy Role Sensory Stimulus Synapses System Tadpoles Tectum Mesencephali Testing Translations Untranslated RNA Visual Visual System Visual impairment Western Blotting Xenopus Xenopus laevis avoidance behavior behavioral plasticity cohort developmental disease experience experimental study flexibility genetic manipulation in vivo in vivo imaging injured injury recovery insight multidisciplinary mutant neural circuit neurological rehabilitation newborn neuron novel repaired response structural imaging superior colliculus Corpora quadrigemina synaptic function treatment strategy visual motor

项目摘要

Brain activity is essential for the development and plasticity of neurons and circuits, however our understanding of the mechanisms by which activity generates functional circuits is incomplete. This lack of knowledge impedes our ability to take advantage of activity-dependent mechanisms to facilitate circuit plasticity. Plasticity-inducing stimuli induce neuronal protein dynamics, including regulated increases and decreases in protein synthesis. We recently conducted a quantitative in vivo proteomic analysis which identified changes in newly synthesized proteins in the Xenopus tadpole visual system in response to plasticity-inducing visual stimulation. We identified numerous candidate plasticity proteins (CPPs), including several that regulate protein synthesis, whereas others have diverse cellular and synaptic functions. Here we will probe the model that plasticity-inducing stimuli initiate a cascade of protein synthesis-dependent events, beginning with de novo synthesis of upstream translational regulators and culminating in the regulated synthesis of diverse effector proteins, in visual experience dependent circuit plasticity in Xenopus, using proteomics, electrophysiology, in vivo structural and functional imaging, and behavioral assays. Classical studies have revealed circuit-rewiring events in response to CNS damage. We have shown that local damage to the optic tectum impairs visual avoidance behavior in Xenopus and that treating injured animals with brief bouts of visual experience facilitates recovery of the injured circuit. To probe the flexibility of experience-dependent plasticity mechanisms, we will test whether newly synthesized candidate plasticity proteins are required for the visual experience-dependent rehabilitation of the injured visuomotor circuit. Results of these experiments may identify novel mechanisms contributing to experience-dependent plasticity in developing nervous systems.

大脑活动对神经元和神经回路的发育和可塑性至关重要