Diversity Supplement: Mechanisms of striatal structural and functional plasticity

多样性补充：纹状体结构和功能可塑性机制

• 批准号: 10302649
• 负责人: YEVGENIA KOZOROVITSKIY
• 金额: $ 1.36万
• 依托单位: NORTHWESTERN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-01 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10302649
• 关键词: Administrative Supplement; Age; Architecture; Basic Science; Brain; Corpus striatum structure; Custom; Dendritic Spines; Development; Disease; Foundations; Glutamates; Image; Laser Microscopy; Lasers; Learning; Light; Membrane; Microscopy; Neurons; Organism; Property; Research Personnel; Sex Differences; Signal Transduction; Structure; Synapses; Therapeutic Agents; Vertebral column; Work; career development; cell type; functional plasticity; innovation; insight; neuroregulation; postsynaptic; reconstruction; research and development; sex; therapy design; two-photon; undergraduate student

PROJECT SUMMARY Dendritic spines are the remarkable, specialized membrane compartments on neurons that house the postsynaptic, receiving end of most excitatory, glutamatergic synapses in the brain. They are highly plastic and change during development, learning, and in disease. This proposal relies on multi-laser 2-photon imaging and photostimulation approaches to generate and evaluate new connections on genetically targeted striatal neurons, dissecting interacting variables of sex, age, and neuromodulatory state. The proposal builds on preliminary observations of sex differences in spinogenesis, which may interact with other convergent signaling cascades to control dendritic spine formation and sensitivity to therapeutic agents. The proposed work would yield valuable insights into new spine and synapse genesis, early-stage function, and stability, impacting basic research relevant to synaptic development and rules that guide plasticity. The resulting platform will help to drive technical innovation that would allow researchers to design therapies to augment reconstruction of neuronal architecture or deconstruct aberrant connectivity. The current supplement introduces a new form of imaging to the project, while supporting a promising undergraduate student in research and career development.

项目概要 树突棘是神经元上非凡的、专门的膜室，它容纳 突触后，大脑中大多数兴奋性谷氨酸突触的接收端。他们是 在发育、学习和疾病过程中具有高度可塑性和变化性。该提案依赖于 多激光 2 光子成像和光刺激方法来生成和评估新的 基因靶向纹状体神经元的连接，剖析性别、年龄、 和神经调节状态。该提案建立在对性别差异的初步观察基础上 棘发生，可能与其他汇聚信号级联相互作用以控制树突 脊柱的形成和对治疗药物的敏感性。拟议的工作将产生有价值的成果 对新脊柱和突触发生、早期功能和稳定性的见解，影响基本 与突触发育和指导可塑性规则相关的研究。由此产生的平台 将有助于推动技术创新，使研究人员能够设计疗法来增强 重建神经元结构或解构异常连接。目前的 补充为该项目引入了一种新的成像形式，同时支持有前途的 研究和职业发展的本科生。