# High Spatiotemporal Resolution Neural Recording System Using Active Sensing

> **NIH NIH R44** · PHYSICAL SCIENCES, INC · 2022 · $890,292

## Abstract

Project Summary/Abstract
The investigation of the complex neural dynamics and the cognitive functions of the brain requires non-
invasive recording tools with high spatial and temporal resolution. Fluorescence imaging/microscopy is one
of the state-of-the-art technologies for high spatial resolution recording of the activity of neuron populations.
However, existing fluorescence neural imaging technologies generally have limited speed, providing less
than a few hundred frames per second (or several milliseconds temporal resolution). This is not only limited
by the technology barriers (e.g. the low speed of cameras and/or beam scanners), but also constrained by
the low signal level emitted by the delicate micro-scale neuronal structures. The milliseconds or slower
temporal resolution substantially precludes measuring the precise timing of the generation and propagation
of neuron spikes, which is the key component of neural signaling. During this R&D program, Physical
Sciences Inc. (PSI), Dartmouth College, and the Broad Institute of MIT and Harvard propose to
develop and demonstrate a novel fluorescence neural imaging technology that enables high-speed
recording of membrane potentials from multiple neurons. This technology combines two complementary
imaging channels to achieve parallel neuronal recording with both sub-micron spatial and sub-millisecond
temporal resolution. The high-speed recording function is achieved using a novel imaging technique based
on a high-sensitivity single-point detector and a high-speed spatial light modulator (SLM). During the Phase I,
we demonstrated the feasibility of the technology by imaging cultured neurons labeled with calcium and
voltage indicating fluorescent sensors. During the proposed Phase II, we will upgrade the technology and
further demonstrate its value in neuroscience investigations. The Phase II prototypes will include a universal
high spatiotemporal resolution sensor that is compatible with various imaging setups including head-mounted
fluorescence mini-microscopes. Two Phase II prototypes will be delivered to collaborating institutes for
performance testing. The testing experiments will focus on demonstrating high spatiotemporal resolution
recording of fast action potentials from both neuron somas in the brain in vivo and sub-cellular structures
(e.g., dendrites and synapses) of neuron cultures or brain slices using genetically encoded voltage sensors.
This R&D project will result in a robust technology for non-invasive recording of neuronal kinetics with high
spatiotemporal resolution, offering a greatly needed tool in the neuroscience field.

## Key facts

- **NIH application ID:** 10481444
- **Project number:** 2R44MH116748-02A1
- **Recipient organization:** PHYSICAL SCIENCES, INC
- **Principal Investigator:** Youbo Zhao
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $890,292
- **Award type:** 2
- **Project period:** 2018-05-01 → 2024-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10481444

## Citation

> US National Institutes of Health, RePORTER application 10481444, High Spatiotemporal Resolution Neural Recording System Using Active Sensing (2R44MH116748-02A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10481444. Licensed CC0.

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