Elucidating the Wiring and Rewiring of Poly-synaptic Memory Circuits by Directed Stepwise Trans-neuronal Tracing

通过定向逐步跨神经元追踪阐明多突触记忆电路的布线和重新布线

• 批准号: 10317095
• 负责人: Wei Xu
• 金额: $ 40.5万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-15 至 2023-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10317095
• 关键词: Anatomy; Animals; Behavior; Brain; Brain Diseases; Brain region; Extinction (Psychology); Functional Imaging; Future; Head; Heterogeneity; Hippocampus (Brain); Interneurons; Investigation; Learning; Learning Disorders; Maps; Memory; Memory Disorders; Methodology; Methods; Microscope; Modification; Monitor; Mus; Neurobiology; Neurons; Neurosciences; Neurosciences Research; Output; Pathway interactions; Pharmacogenetics; Population; Process; Property; Proteins; Regulation; Retrieval; Sensory; Series; Sum; Synapses; Testing; Time; Tracer; Viral; Viral Vector; Virus; association cortex; cell type; interest; memory encoding; multimodality; neural circuit; neuronal circuitry; new technology; novel; optogenetics; sensory cortex; technology development; tool

Summary Multimodal sensory information is converged through poly-synaptic pathways to the hippocampus to form integrated representations and encode memories of the world, which in turn guide our future behavior through multiple poly-synaptic downstream pathways. It is well known that each of the brain regions in this circuit consists of various neuronal cell types or groups which are distinct in connectivity and functions. Yet we cannot construct a long-range poly-synaptic wring diagram among these specific neuronal groups without efficient tools to continuously track the multiple orders of synaptic connections in a controlled and directed manner. Similarly, it is not clear if the wiring of this pathway is subject to dynamic modifications by learning, memory or brain disorders due to a lack of tools to continuously monitor the neuronal connectivity over time. Here we propose to develop novel methodology to embrace these challenges. In the first part we will modify viral vectors for trans-neuronal tracing which can spread across synapses in a controlled, stepwise manner. With the new tool we will test the hypothesis that distinct neuronal groups in the CA1 or CA3 regions of the hippocampus receive distinct poly-synaptic inputs and send out distinct poly-synaptic outputs. In the second part we will conduct functional imaging and functional manipulations of the specific CA1 or CA3 neuronal groups to test the hypothesis that these neuronal groups, defined by their specific poly-synaptic inputs and/or outputs, receive distinct sensory information and in turn adjust different aspects of behavior. In the third part we will develop novel technology to trace in the same animal the connectivity of neurons of interest at two time points--before and after a learning process--to examine if learning and memory alters neuronal connectivity. Together, these studies will demonstrate whether the distinct neuronal groups at each brain region in the memory circuit are selectively connected with specific neuronal groups in other brain regions to form functional “channels” which bridge different sensory information to the different aspects of behavior. The novel tools to be developed/optimized in this study will find wide use in neuroscience research helping us to map out the functional network in the brain.

概括 多模态感觉信息通过多突触通路汇聚到 海马体形成整合的表征并编码世界的记忆， 通过多个多突触下游通路来指导我们未来的行为，这很好。 已知该回路中的每个大脑区域都由各种神经元细胞类型或 然而，我们无法构建一个远程的群体。 这些特定神经群之间的多突触接线图，没有有效的工具来 以受控和定向的方式连续跟踪突触连接的多个顺序 同样，尚不清楚该通路的布线是否会受到动态修改 由于缺乏持续监控工具而导致学习、记忆或大脑障碍 在这里，我们建议开发新的方法来接受。 在第一部分中，我们将修改用于跨神经元追踪的病毒载体。 使用我们将测试的新工具，可以以受控的、逐步的方式在突触上传播。 假设海马 CA1 或 CA3 区域有不同的神经群 在第二个阶段接收不同的多突触输入并发出不同的多突触输出。 我们将对特定 CA1 或 CA3 进行功能成像和功能操作 神经组来检验以下假设：这些神经组由其特定的定义 多突触输入和/或输出，接收不同的感觉信息并依次调整 在第三部分中，我们将开发新的技术来追踪行为的不同方面。 同一动物的感兴趣神经元在两个时间点（之前和之后）的连接性 学习过程——检查学习和记忆是否一起改变神经连接。 这些研究将证明每个大脑区域的不同神经群是否 记忆回路有选择地与其他大脑区域的特定神经群连接， 形成功能性“通道”，将不同的感官信息与事物的不同方面联系起来 本研究中开发/优化的新颖工具将在以下领域得到广泛应用。 神经科学研究帮助我们绘制大脑的功能网络。

项目成果

Anterograde transneuronal tracing and genetic control with engineered yellow fever vaccine YFV-17D.

使用工程黄热病疫苗 YFV-17D 进行顺行跨神经元追踪和遗传控制。

• 发表时间: 2021-12
• 影响因子: 48
• 作者: Li, Elizabeth;Guo, Jun;Oh, So Jung;Luo, Yi;Oliveros, Heankel Cantu;Du, Wenqin;Arano, Rachel;Kim, Yerim;Chen, Yuh;Eitson, Jennifer;Lin, Da;Li, Ying;Roberts, Todd;Schoggins, John W;Xu, Wei
• 通讯作者: Xu, Wei

Inhibitory hippocampus-medial septum projection controls locomotion and exploratory behavior.

抑制性海马-内侧隔膜投射控制运动和探索行为。

• 发表时间: 2023
• 作者: Chen, Yuh;Arano, Rachel;Guo, Jun;Saleem, Uzair;Li, Ying;Xu, Wei
• 通讯作者: Xu, Wei

Directed stepwise tracing of polysynaptic neuronal circuits with replication-deficient pseudorabies virus.

使用复制缺陷型伪狂犬病病毒对多突触神经元回路进行定向逐步追踪。

• 发表时间: 2023-06-26
• 作者: Du, Wenqin;Li, Elizabeth;Guo, Jun;Arano, Rachel;Kim, Yerim;Chen, Yuh;Thompson, Alyssa;Oh, So Jung;Samuel, Aspen;Li, Ying;Oyibo, Hassana K;Xu, Wei
• 通讯作者: Xu, Wei