Developing Novel Trans-Synaptic Viral Vectors for Orthogonal or Rapid Circuit Tracing

开发用于正交或快速电路追踪的新型跨突触病毒载体

• 批准号: 10640622
• 负责人: Euiseok J Kim
• 金额: $ 112.93万
• 依托单位: UNIVERSITY OF CALIFORNIA SANTA CRUZ
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2026-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10640622
• 关键词: Anatomy; Animal Behavior; Animals; Area; Bar Codes; Behavior; Brain; Brain Diseases; Cells; Complex; Corpus striatum structure; Development; Disadvantaged; Electronic Medical Records and Genomics Network; Engineering; Gene Expression; Genomics; Glycoproteins; Hippocampus; Interneurons; Label; Learning; Methods; Mission; Modeling; Monitor; Mus; Neurodevelopmental Disorder; Neuronal Plasticity; Neurons; Neurosciences; Organizational Productivity; Outcomes Research; Output; Parvalbumins; Perception; Population; Process; RNA Viruses; Rabies; Rabies virus; Rattus; Research; Schizophrenia; Sendai virus; Slice; Specificity; Synapses; System; Target Populations; Techniques; Therapeutic; Tracer; United States National Institutes of Health; Variant; Viral; Viral Vector; Virus; Visualization; autism spectrum disorder; cell type; cholinergic; design; experimental study; in vivo; innovation; neural; neural circuit; novel; presynaptic; presynaptic neurons; prevent; public health relevance; rabies viral tracing; temperature sensitive mutant; therapeutic target; timeline; tool; vector; virus genetics

Project Summary To determine the anatomical basis of complex neural behavior, it is critical to have the ability to trace more than one circuit simultaneously in the same animal. That’s because complex animal behaviors or neural computation should be understood through the interaction of more than one circuit – cooperative, antagonistic, or else. In addition, it is necessary to rapidly capture the connectivity information in the dynamically changing brains during development and learning. Engineered G-deleted rabies is a current state-of-art method to retrogradely trace the presynaptic input neurons of a defined cell type. However, it remains unfeasible to trace more than one neural circuit simultaneously. In addition, the current approach using AAV helpers and rabies requires several weeks for tracing. In this proposed research, we will overcome these disadvantages by developing two novel trans-synaptic viral tracer systems: SWORD: Sendai with Orthogonal Rabies Duplex Tracing (Aim 1) and a rapid TRIO/cTRIO: cell-type specific tracing the relationship between input and output (Aim 2). This research is significant because these new methods will allow more comprehensive analysis of neural connectivity in more than one circuit and in more diverse context such as the developing brain where distinct synaptic networks emerge and neural plasticity such as learning across many model species. The proposed research is innovative, because we are developing and validating technically innovative solutions, SWORD and rapid TRIO/cTRIO, to overcome the limitations of the current state-of-the art tracing method. These viral-genetic tools will have a positive and broad impact on the neuroscience field as it will enhance our understanding of neural circuit organization for the complex behaviors and help to identify the circuit-specific therapeutic targets to cure brain disorders.

项目摘要 为了确定复杂神经行为的解剖基础，至关重要 仅在同一动物中追踪多个电路。那是因为复杂的动物 行为或神经计算应通过多个相互作用来理解 电路 - 合作，对立，否则。另外，有必要快速捕获 在开发和学习过程中动态变化的大脑中的连通性信息。 工程G污染的狂犬病是逆行追踪突触的当前最新方法 定义细胞类型的输入神经元。但是，追踪多个神经元仍然是不可行的 简单的电路。此外，使用AAV助手和狂犬病的当前方法需要 跟踪数周。在这项拟议的研究中，我们将通过 开发两个新型的跨突触病毒示踪系统：剑：仙台与正交 狂犬病双链示踪（AIM 1）和快速的三重奏/ctrio：细胞类型特异性跟踪关系 在输入和输出之间（AIM 2）。这项研究很重要，因为这些新方法将 在多个电路和更多电路中对神经连通性进行更全面的分析 潜水的环境，例如发展中的大脑，其中明显的突触网络出现和中性 可塑性，例如在许多模型物种中学习。拟议的研究是创新的， 因为我们正在开发和验证技术创新的解决方案，剑和快速 三重奏/ctrio，以克服当前最新示踪方法的局限性。这些 病毒遗传工具将对神经科学领域产生积极和广泛的影响 增强我们对神经电路组织对复杂行为的理解，并有助于 确定特定电路的治疗靶标，以治愈脑疾病。