# Brain-wide Neuronal Circuit Mapping with X-ray Nano-Holography

> **NIH NIH R00** · YALE UNIVERSITY · 2023 · $248,902

## Abstract

Project Summary
This proposal's objective is to develop synchrotron-based X-ray imaging technologies to enable high-resolution imaging
of brain-wide neuronal circuits. Comprehensively mapping brain-wide circuits is not currently feasible, even in small
mammalian model systems, because light microscopy (LM) lacks sufficient resolution and electron microscopy (EM)
cannot be applied over large volumes. Leveraging the unprecedented qualities of the new 4th generation synchrotron
source at the European Synchrotron, we will develop X-ray nano-holography (XNH) imaging techniques for large-scale
imaging of brain circuits. Taking advantage of improvements in source coherence and brightness, we will improve
imaging resolution to allow direct visualization of synaptic connections between neurons, and develop imaging protocols
that allow imaging of centimeter-scale circuit volumes within a typical beamline experiment. We will combine non-
destructive XNH with EM and LM imaging techniques to rigorously and quantitatively validate the accuracy of XNH-
based circuit reconstruction. We will then use this correlative workflow to study the relationships between long-range
sensory inputs, local synaptic micro-circuitry, and single-neuron activity, investigating how circuits in the posterior
parietal cortex (PPC) support perceptual decision-making. Lastly, we will apply XNH circuit-mapping over an entire
cortical hemisphere, and utilize deep-learning based machine vision algorithms to obtain a comprehensive atlas of cortical
connectivity. This atlas will in principle resolve all long-range connections between cortical areas at single-axon
resolution, lending insight into how distinct cortical areas achieve specialized function, and how distributed cortical
networks support cognition and are affected by psychiatric disorders.

## Key facts

- **NIH application ID:** 10877549
- **Project number:** 4R00EB032217-03
- **Recipient organization:** YALE UNIVERSITY
- **Principal Investigator:** Aaron Kuan
- **Activity code:** R00 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $248,902
- **Award type:** 4N
- **Project period:** 2023-09-01 → 2026-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10877549

## Citation

> US National Institutes of Health, RePORTER application 10877549, Brain-wide Neuronal Circuit Mapping with X-ray Nano-Holography (4R00EB032217-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10877549. Licensed CC0.

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