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

基本信息

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
项目类别：
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

项目摘要

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.

概括多模式的感觉信息通过多突触途径收敛到海马形成综合表示并编码世界的记忆通过多种多突触下游途径指导我们的未来行为。很好知道该电路中的每个大脑区域都由各种神经元细胞类型或在连接性和功能上不同的组。但是我们不能构建一个远程这些特定神经元组之间的多突触包裹图，没有有效的工具连续跟踪受控和定向中的多个突触连接的顺序方式。同样，尚不清楚该途径的接线是否受到动态修改由于缺乏连续监视的工具，通过学习，记忆或脑部疾病随着时间的流逝，神经元连通性。在这里，我们建议开发新的方法来拥抱这些挑战。在第一部分中，我们将修改病毒向量以进行跨神经元跟踪可以以受控的逐步方式散布突触。使用新工具，我们将测试海马的CA1或CA3区域中不同的神经元基团的假设接收不同的多突触输入，并发送不同的多突触输出。在第二个我们将进行特定CA1或CA3的功能成像和功能操纵神经元组测试这些神经元基团的假设多突触输入和/或输出，接收不同的感官信息，然后调整行为的不同方面。在第三部分中，我们将开发新技术来追踪同一动物在两个时间点 - 之前和之后，感兴趣的神经元的连通性学习过程 - 检查学习和记忆是否会改变神经元连接。一起，这些研究将证明是否在每个大脑区域的不同神经元组是否记忆电路选择性地与其他大脑区域的特定神经元组连接到形成功能“渠道”，将不同的感官信息桥接到行为。在本研究中要开发/优化的新颖工具将在神经科学研究有助于我们绘制大脑中的功能网络。

项目成果

期刊论文数量（3）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

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

DOI：
10.1016/j.crmeth.2023.100506
发表时间：
2023-06-26
期刊：
Cell reports methods
影响因子：
0
作者：
通讯作者：

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

DOI：
10.3389/fnsyn.2023.1042858
发表时间：
2023
期刊：
FRONTIERS IN SYNAPTIC NEUROSCIENCE
影响因子：
3.7
作者：
Chen, Yuh-Tarng;Arano, Rachel;Guo, Jun;Saleem, Uzair;Li, Ying;Xu, Wei
通讯作者：
Xu, Wei

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

DOI：
10.1038/s41592-021-01319-9
发表时间：
2021-12
期刊：
Nature methods
影响因子：
48
作者：
Li E;Guo J;Oh SJ;Luo Y;Oliveros HC;Du W;Arano R;Kim Y;Chen YT;Eitson J;Lin DT;Li Y;Roberts T;Schoggins JW;Xu W
通讯作者：
Xu W