Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans

Jeffrey P. Nguyen, Frederick B. Shipley, Ashley N. Linder, George S. Plummer, Mochi Liu, Sagar U. Setru, Joshua William Shaevitz, Andrew Michael Leifer

Research output: Contribution to journalArticle

76 Citations (Scopus)

Abstract

The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal's position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocalmicroscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal's position and orientation. Custom software tracks the 3D position of the animal's head in real time and two feedback loops adjust a motorized stage and objective to keep the animal's head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal's behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.

Original languageEnglish (US)
Pages (from-to)E1074-E1081
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number8
DOIs
StatePublished - Feb 23 2016

Fingerprint

Caenorhabditis elegans
Neuroimaging
Calcium
Neurons
Head
Animal Behavior
Locomotion
Aptitude
Posture
Noise
Software
Fluorescence
Population

All Science Journal Classification (ASJC) codes

  • General

Cite this

Nguyen, Jeffrey P. ; Shipley, Frederick B. ; Linder, Ashley N. ; Plummer, George S. ; Liu, Mochi ; Setru, Sagar U. ; Shaevitz, Joshua William ; Leifer, Andrew Michael. / Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 8. pp. E1074-E1081.
@article{869fc660a27c45ee9b7e077547d03672,
title = "Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans",
abstract = "The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal's position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocalmicroscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal's position and orientation. Custom software tracks the 3D position of the animal's head in real time and two feedback loops adjust a motorized stage and objective to keep the animal's head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal's behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.",
author = "Nguyen, {Jeffrey P.} and Shipley, {Frederick B.} and Linder, {Ashley N.} and Plummer, {George S.} and Mochi Liu and Setru, {Sagar U.} and Shaevitz, {Joshua William} and Leifer, {Andrew Michael}",
year = "2016",
month = "2",
day = "23",
doi = "https://doi.org/10.1073/pnas.1507110112",
language = "English (US)",
volume = "113",
pages = "E1074--E1081",
journal = "Proceedings of the National Academy of Sciences of the United States of America",
issn = "0027-8424",
number = "8",

}

Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans. / Nguyen, Jeffrey P.; Shipley, Frederick B.; Linder, Ashley N.; Plummer, George S.; Liu, Mochi; Setru, Sagar U.; Shaevitz, Joshua William; Leifer, Andrew Michael.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 8, 23.02.2016, p. E1074-E1081.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Whole-brain calcium imaging with cellular resolution in freely behaving Caenorhabditis elegans

AU - Nguyen, Jeffrey P.

AU - Shipley, Frederick B.

AU - Linder, Ashley N.

AU - Plummer, George S.

AU - Liu, Mochi

AU - Setru, Sagar U.

AU - Shaevitz, Joshua William

AU - Leifer, Andrew Michael

PY - 2016/2/23

Y1 - 2016/2/23

N2 - The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal's position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocalmicroscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal's position and orientation. Custom software tracks the 3D position of the animal's head in real time and two feedback loops adjust a motorized stage and objective to keep the animal's head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal's behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.

AB - The ability to acquire large-scale recordings of neuronal activity in awake and unrestrained animals is needed to provide new insights into how populations of neurons generate animal behavior. We present an instrument capable of recording intracellular calcium transients from the majority of neurons in the head of a freely behaving Caenorhabditis elegans with cellular resolution while simultaneously recording the animal's position, posture, and locomotion. This instrument provides whole-brain imaging with cellular resolution in an unrestrained and behaving animal. We use spinning-disk confocalmicroscopy to capture 3D volumetric fluorescent images of neurons expressing the calcium indicator GCaMP6s at 6 head-volumes/s. A suite of three cameras monitor neuronal fluorescence and the animal's position and orientation. Custom software tracks the 3D position of the animal's head in real time and two feedback loops adjust a motorized stage and objective to keep the animal's head within the field of view as the animal roams freely. We observe calcium transients from up to 77 neurons for over 4 min and correlate this activity with the animal's behavior. We characterize noise in the system due to animal motion and show that, across worms, multiple neurons show significant correlations with modes of behavior corresponding to forward, backward, and turning locomotion.

UR - http://www.scopus.com/inward/record.url?scp=84959230958&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959230958&partnerID=8YFLogxK

U2 - https://doi.org/10.1073/pnas.1507110112

DO - https://doi.org/10.1073/pnas.1507110112

M3 - Article

VL - 113

SP - E1074-E1081

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

SN - 0027-8424

IS - 8

ER -