# High-throughput mapping of synaptic connectivity between transcriptomically defined cell types

> **NIH NIH RF1** · BOSTON UNIVERSITY (CHARLES RIVER CAMPUS) · 2022 · $1,423,833

## Abstract

PROJECT SUMMARY
Identifying the cell types that make up each region of the brain and the patterns of synaptic connections
through which they are linked is key to understanding how neural circuits give rise to all perception, cognition,
and behavior. Rapid improvements in optical, molecular, and computational technologies are enabling large-
scale projects aiming to comprehensively map the cell types that comprise the mammalian brain.
Nevertheless, defining the microconnectivity of the thousands of cell types in the brain remains challenging
due to a lack of scalable methods. This proposal describes the development of a technology for addressing this
methodological gap. Using a novel combination of high-sensitivity fluorescence voltage imaging and single-
neuron optogenetic photostimulation, we will map synaptic connectivity within – and between – brain regions.
Using this approach, synaptic connectivity can be mapped with throughput two to three orders of magnitude
higher than existing techniques. Importantly, leveraging an all-optical approach to mapping connectivity will
allow us integrate synaptic connectivity measurements with emerging techniques for highly multiplexed
fluorescence in situ hybridization. In this way, we can identify the molecular identities of large neuronal
populations and their connectivity. We will demonstrate the technology developed in this proposal in the
motor cortex, a region where knowledge of gene expression patterns has far outpaced our ability to identify
connectivity motifs. Revealing both local connectivity motifs and the precise molecular identity of cells that
receive long-range input from the thalamus – an important driver of cortical activity – will provide new
insights into the circuit mechanisms supporting voluntary movements.

## Key facts

- **NIH application ID:** 10413540
- **Project number:** 1RF1MH126882-01A1
- **Recipient organization:** BOSTON UNIVERSITY (CHARLES RIVER CAMPUS)
- **Principal Investigator:** Michael Nicholas Economo
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $1,423,833
- **Award type:** 1
- **Project period:** 2022-05-01 → 2026-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10413540

## Citation

> US National Institutes of Health, RePORTER application 10413540, High-throughput mapping of synaptic connectivity between transcriptomically defined cell types (1RF1MH126882-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10413540. Licensed CC0.

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