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

> **NIH NIH R01** · UT SOUTHWESTERN MEDICAL CENTER · 2020 · $405,000

## Abstract

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.

## Key facts

- **NIH application ID:** 9829591
- **Project number:** 5R01NS104828-03
- **Recipient organization:** UT SOUTHWESTERN MEDICAL CENTER
- **Principal Investigator:** Wei Xu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $405,000
- **Award type:** 5
- **Project period:** 2017-12-15 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9829591

## Citation

> US National Institutes of Health, RePORTER application 9829591, Elucidating the Wiring and Rewiring of Poly-synaptic Memory Circuits by Directed Stepwise Trans-neuronal Tracing (5R01NS104828-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9829591. Licensed CC0.

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