# Pan-neuronal functional imaging and anesthesia

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $313,500

## Abstract

Abstract
Volatile anesthetics produce all stages of general anesthesia including unconsciousness, amnesia, analgesia
and muscle relaxation. Once placed into this physiological state, the experience, memory and physical
response to excruciating pain are all lost. However, we still do not understand mechanistically how this state of
anesthesia is produced within neuronal systems such that complex mental activity is ablated while vestigial
physiology is preserved. To date, research has proceeded along essentially two tracks: either the gross
measurement of neuronal activity in entire regions of the brain using fMRI and EEG (which are fundamentally
limited by resolution), or analysis at the molecular level looking for specific receptors for the volatile anesthetics
(which has largely foundered). Astonishingly, patients can nevertheless be promptly retrieved from this state,
and empirical clinical practice has reduced the risk of anesthesia to the extent that it is now an essential and
universally accepted part of the modern practice of medicine. Fortunately, using novel fluorescent microscopy,
we are now able to image neuronal activity in real-time, in vivo, and at resolutions capable of simultaneously
capturing the activity of individual neurons and entire populations of complex neuronal networks. In this study,
we apply this technique to C. elegans in which we are able to capture the activity of the entire nervous system,
and to the mouse in which we capture regions of the somatosensory cortex. To discern the effect by which
clinical anesthesia is achieved, it would make sense to begin with the creature with the simplest, most tractable
neuronal architecture in which anesthesia is known to be inducible. C. elegans offers a simple well-mapped
nervous system (302 neurons), well characterized behavioral paradigms and amenable genetics. Moreover C.
elegans is well established as a model system in anesthesiology, and displays distinct stages of gross
behavior under anesthesia similar to humans. Using GCaMP, a fluorescent indicator of intracellular calcium
concentration expressed transgenically under a neuronal promoter, we can capture the activity of multiple
neurons optically, non-invasively, and in parallel. Our experimental system will allow us to measure activity of
the individual neurons within large-scale neuronal circuits to understand how subtle modifications in discrete
neuronal dynamics lead to the gross but reversible functional defects at the level of the overall nervous system
that result in analgesia and physical quiescence. Our study will define the effects of volatile anesthetics over
increasing neuronal complexity from individual neurons to the entire nervous system. Current technology within
mammalian systems is limited in scale to small subsections of the brain. We will begin complementary
imaging experiments in the somatosensory cortex of the mouse that will initiate the translation of our findings
and techniques to mammalian systems...

## Key facts

- **NIH application ID:** 10252010
- **Project number:** 5R01GM121457-05
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Christopher W Connor
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $313,500
- **Award type:** 5
- **Project period:** 2017-09-15 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10252010

## Citation

> US National Institutes of Health, RePORTER application 10252010, Pan-neuronal functional imaging and anesthesia (5R01GM121457-05). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10252010. Licensed CC0.

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