Mechanisms of adult forebrain neural circuit regeneration

成人前脑神经回路再生机制

• 批准号: 10362563
• 负责人: DAVID J PERKEL
• 金额: $ 51.05万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-05-15 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10362563
• 关键词: Acoustics; Adult; Agonist; Alzheimer' s Disease; Behavior; Behavioral; Birds; Birth; Brain; Brain-Derived Neurotrophic Factor; Breeding; Calcium; Calcium Channel; Cell Nucleus; Cells; Cessation of life; Collaborations; Complex; Degenerative Disorder; Electrophysiology (science); Endocrinology; Ensure; Genes; Goals; Growth Associated Protein 43; Hormones; Human; Lead; Link; Maintenance; Mediating; Modeling; Molecular; Molecular Biology; Motor Skills; Muscimol; Natural regeneration; Nervous System Trauma; Neuronal Dysfunction; Neuronal Plasticity; Neurons; Newborn Infant; Outcome; Parkinson Disease; Performance; Potassium Channel; Prosencephalon; Proteins; Public Health; Recombinants; Regulation; Research; Research Personnel; Role; Route; Signal Pathway; Signal Transduction; Sparrows; Stroke; Structure; Synapses; System; Testing; Testosterone; Therapeutic; Therapeutic Intervention; Trauma; adult neurogenesis; antagonist; axon growth; bird song; brain repair; cyclopamine; experience; experimental study; inhibitor; injury and repair; interdisciplinary approach; male; migration; morphometry; nervous system disorder; neural circuit; neuroblast; neurogenesis; neuronal cell body; neurophysiology; neurotrophic factor; newborn neuron; postsynaptic; presynaptic; prevent; programs; receptor; reconstruction; repaired; response; stem cells; stereotypy; steroid hormone

Project Summary: The neural circuit that regulates birdsong, a highly precise, learned sensorimotor behavior, excels for study of fundamental mechanisms of adult circuit plasticity. The song system is a unique model of naturally occurring degeneration and compensatory regeneration in a behaviorally relevant neural circuit in adult brains. This circuit shows exaggerated seasonal degeneration and reconstruction via neurogenesis, in response to changes in circulating steroid hormone levels. Our long-term goal is to understand the fundamental mechanisms by which steroid hormones and neurotrophins interact to regulate plasticity of neural circuits and behavior. On a translational level, our goal is to understand how forebrain circuits can regenerate to support performance of complex learned motor skills. The central hypothesis of the proposed aims is that seasonal changes in hormones trigger changes in anterograde and retrograde trophic signaling that lead to remodeling of the HVC-RA circuit and changes in song behavior in adult birds.The goal of this application is to identify the trophic signaling pathways (molecular and electrophysiological) that regulate the the incorporation of newborn neurons to regenerate this circuit. This research will advance the field by elucidating fundamental issues of adult circuit plasticity. This topic is of translational relevance for exploiting endogenous or exogenous stem cells for therapeutic repair of injured or dysfunctional circuits in humans. These fundamental issues include whether new neurons added to adult circuits establish functional connections with efferent nuclei and restore behavior (Aim 1), the role of activity regulated genes in mediating retrograde trophic effects of neuronal activity on presynaptic adult neurogenesis (Aim 2), the role of calcium channels in mediating the transsynaptic neurotrophic regulation of postsynaptic activity (Aim 3), and the role of pre- and/or postsynaptic neuronal activity in maintaining a regenerated adult circuit (Aim 4).

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