# Close-loop, spatially addressable multiphoton functional imaging

> **NIH NIH U01** · CORNELL UNIVERSITY · 2021 · $609,470

## Abstract

Abstract
 A major goal of brain research is to image the dynamics of groups of neurons during behavior. Although
even the simplest behaviors involve interactions across multiple parts of the nervous system, our tools for
assessing function at the level of individual neurons usually allow only access to small regions of the brain, and
with limited temporal resolution. Optical recordings of activity are critical to probe neural systems because they
provide high-resolution, non-invasive measurements, ranging from single neurons to entire populations in intact
nervous systems, and are readily combined with genetic methods to provide cell type-specific recordings.
Nevertheless, the limited spatial scale and temporal resolution remain a major challenge for optical imaging.
Cellular-resolution imaging in scattering brains is typically achieved with multiphoton microscopy (MPM). The
focus of this proposal is to develop, implement, and disseminate a new generation of multiphoton imaging tools
and genetically encoded indicators that allow deep, fast, and large-scale imaging of structure and function with
cellular and subcellular resolution. To approach fundamental limits defined by the 'photon budget', we will
develop an adaptive excitation source (AES). By feeding the structural information of the sample to the source,
and synchronizing the on-demand pulses with the microscope scanning system, the AES transforms a
conventional MPM into a “random-access” MPM that only excites regions of interest. We will integrate the AES
with high speed scanners, resulting in a new AES-MPM that will provide >10x improvement in imaging speed or
the number of neurons imaged. We will combine the AES effort at Cornell with the development effort of
genetically encoded voltage indicator (GEVI) at Stanford and Janelia Research Campus, and demonstrate the
AES-MPM in imaging GEVI labeled neurons in mouse brains in vivo. We will also combine the AES with a
multiphoton mesoscope to demonstrate large scale imaging of genetically encoded Ca indicator (GECI). The
research involves close interactions between the PI (Xu), Co-investigator Michael Lin (Stanford), and Karel
Svoboda (Janelia). Furthermore, the investigators will work closely with industrial partners to explore the potential
of translating the AES into a commercially available system, which provides a direct path to broad dissemination.

## Key facts

- **NIH application ID:** 10246271
- **Project number:** 5U01NS113281-03
- **Recipient organization:** CORNELL UNIVERSITY
- **Principal Investigator:** CHRIS XU
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $609,470
- **Award type:** 5
- **Project period:** 2019-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10246271

## Citation

> US National Institutes of Health, RePORTER application 10246271, Close-loop, spatially addressable multiphoton functional imaging (5U01NS113281-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10246271. Licensed CC0.

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