# Scalable technologies for brain-wide connectomics of transcriptomic cell types: focus on brainstem

> **NIH NIH RF1** · ALLEN INSTITUTE · 2022 · $4,714,572

## Abstract

Project summary, Scalable technologies for brain-wide connectomics of
transcriptomic cell types: focus on brainstem
This proposal is to develop a scalable pipeline to combine high-resolution morphology and molecular
classification of individual neurons to define morpho-molecular cell types in the brain. Complete morphology of
individual neurons provides insights of connectivity and information processing in the brain and reveals how
neuronal activity is routed across brain areas. Layering transcriptomic information on to morphologically distinct
types provides the basis to access these defined neuron types for functional analysis. Such a combined
classification of the brain’s cell types is foundational for understanding the role of defined neuron types within
neural circuits and how information processing within multi-regional neural circuits orchestrate complex
behaviors.
Sequencing-based approaches have been used to categorize the brain’s cells into transcriptomic types (t-
types) with high throughput. Parallel strategies for a complete description of the morphological types brain-wide
are too slow and methods for a combined analysis of these two modalities are lacking. To address this, we will
create a brain-wide imaging and neuronal reconstruction platform that provides faster imaging using selective
plane illumination microscopy and accelerated reconstructions with modern machine learning tools based on
U-Nets and reinforcement learning. We will combine this with post hoc transcriptomic characterization of
reconstructed cells with multiplexed fluorescent in situ hybridization to define morpho-molecular types.
We will create a data set of 2,000 such dual categorized neuron types from a critical brain area, the medulla, in
the mouse. The medulla is comprised of diverse neuronal types organized in numerous inter-related nuclei
essential for autonomic functions such as breathing, vasomotor control, integration of ascending inputs from
sensory and interoceptive channels and coordination of motor actions such as chewing, licking and swallowing.
Our census of morpho-molecular medullary neuron types will lay the foundation for a systematic cell type
specific functional interrogation of these neurons within brainstem circuits and in the larger context of multi-
regional brain circuits. Furthermore, this will serve as the blueprint for carrying out such studies throughout the
mouse brain, and other brains, including that of primates.

## Key facts

- **NIH application ID:** 10369309
- **Project number:** 1RF1MH128841-01
- **Recipient organization:** ALLEN INSTITUTE
- **Principal Investigator:** Jayaram Chandrashekar
- **Activity code:** RF1 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $4,714,572
- **Award type:** 1
- **Project period:** 2022-03-01 → 2025-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10369309

## Citation

> US National Institutes of Health, RePORTER application 10369309, Scalable technologies for brain-wide connectomics of transcriptomic cell types: focus on brainstem (1RF1MH128841-01). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10369309. Licensed CC0.

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