# High-throughput sequencing of synaptic partnerships and gene expression at single-cell resolution in vivo

> **NIH NIH RF1** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $2,107,104

## Abstract

PROJECT SUMMARY
Brain function depends on forming and maintaining synaptic connections between neurons of specific types,
yet systematic descriptions of cell-type connectivity and the molecules that instruct these relationships remain
challenging because we lack some necessary tools. Traditional approaches for measuring synaptic
connections and networks – such as whole-cell electrophysiology and anatomical reconstructions – sample
only a few cells or small tissue volumes, do not readily scale to many animals or genotypes, and do not
ascertain the molecular type and state of each cell. To bridge this gap, I have developed a barcoded rabies
virus-based method called SBARRO which stores synaptic partnership data in each cells' RNA, allowing
synaptic networks and gene expression to be measured simultaneously in hundreds of thousands of cells
using high-throughput single-cell RNA sequencing. SBARRO experiments in vitro have demonstrated that
quantitative models of cell type-specific connectivity can be systematically generated and used to discover
gene expression signatures associated with connectivity properties. Yet technical limitations related to cell
sampling, recombinant adeno-associated “helper” viruses (rAAVs) and rabies virus biology have precluded
analyses of intact brain tissue.
Here, I propose to address these limitations and advance SBARRO to generate quantitative models of synaptic
networks in vivo based on the following aims: 1) create an anatomically-informed version of SBARRO based
on spatially-resolved single-cell RNA sequencing (called “Slide-SBARRO”); 2) develop a new class of CRE
recombinase-sensitive rAAVs which deliver transgenes while reporting the recombination state of expressed
RNA; and 3) evaluate the synapse-selectivity of rabies virus transmission from postsynaptic to presynaptic
cells. I will focus on mouse striatum because: 1) striatal cell populations are now well-characterized by me and
others; 2) little is known about the synaptic organization of intrinsic striatal cell types and 3) extensive mouse
genetic tools enable Slide-SBARRO connectivity models to be carefully tested through cell-type-specific
anatomy and electrophysiology.

## Key facts

- **NIH application ID:** 10506110
- **Project number:** 1RF1MH130464-01
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** ARPIAR B SAUNDERS
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,107,104
- **Award type:** 1
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10506110

## Citation

> US National Institutes of Health, RePORTER application 10506110, High-throughput sequencing of synaptic partnerships and gene expression at single-cell resolution in vivo (1RF1MH130464-01). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10506110. Licensed CC0.

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