All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals
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All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals. / Bergs, Amelie C F; Liewald, Jana F; Rodriguez-Rozada, Silvia; Liu, Qiang; Wirt, Christin; Bessel, Artur; Zeitzschel, Nadja; Durmaz, Hilal; Nozownik, Adrianna; Dill, Holger; Jospin, Maëlle; Vierock, Johannes; Bargmann, Cornelia I; Hegemann, Peter; Wiegert, J Simon; Gottschalk, Alexander.
In: NAT COMMUN, Vol. 14, No. 1, 06.04.2023, p. 1939.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals
AU - Bergs, Amelie C F
AU - Liewald, Jana F
AU - Rodriguez-Rozada, Silvia
AU - Liu, Qiang
AU - Wirt, Christin
AU - Bessel, Artur
AU - Zeitzschel, Nadja
AU - Durmaz, Hilal
AU - Nozownik, Adrianna
AU - Dill, Holger
AU - Jospin, Maëlle
AU - Vierock, Johannes
AU - Bargmann, Cornelia I
AU - Hegemann, Peter
AU - Wiegert, J Simon
AU - Gottschalk, Alexander
N1 - © 2023. The Author(s).
PY - 2023/4/6
Y1 - 2023/4/6
N2 - Excitable cells can be stimulated or inhibited by optogenetics. Since optogenetic actuation regimes are often static, neurons and circuits can quickly adapt, allowing perturbation, but not true control. Hence, we established an optogenetic voltage-clamp (OVC). The voltage-indicator QuasAr2 provides information for fast, closed-loop optical feedback to the bidirectional optogenetic actuator BiPOLES. Voltage-dependent fluorescence is held within tight margins, thus clamping the cell to distinct potentials. We established the OVC in muscles and neurons of Caenorhabditis elegans, and transferred it to rat hippocampal neurons in slice culture. Fluorescence signals were calibrated to electrically measured potentials, and wavelengths to currents, enabling to determine optical I/V-relationships. The OVC reports on homeostatically altered cellular physiology in mutants and on Ca2+-channel properties, and can dynamically clamp spiking in C. elegans. Combining non-invasive imaging with control capabilities of electrophysiology, the OVC facilitates high-throughput, contact-less electrophysiology in individual cells and paves the way for true optogenetic control in behaving animals.
AB - Excitable cells can be stimulated or inhibited by optogenetics. Since optogenetic actuation regimes are often static, neurons and circuits can quickly adapt, allowing perturbation, but not true control. Hence, we established an optogenetic voltage-clamp (OVC). The voltage-indicator QuasAr2 provides information for fast, closed-loop optical feedback to the bidirectional optogenetic actuator BiPOLES. Voltage-dependent fluorescence is held within tight margins, thus clamping the cell to distinct potentials. We established the OVC in muscles and neurons of Caenorhabditis elegans, and transferred it to rat hippocampal neurons in slice culture. Fluorescence signals were calibrated to electrically measured potentials, and wavelengths to currents, enabling to determine optical I/V-relationships. The OVC reports on homeostatically altered cellular physiology in mutants and on Ca2+-channel properties, and can dynamically clamp spiking in C. elegans. Combining non-invasive imaging with control capabilities of electrophysiology, the OVC facilitates high-throughput, contact-less electrophysiology in individual cells and paves the way for true optogenetic control in behaving animals.
KW - Animals
KW - Rats
KW - Caenorhabditis elegans/physiology
KW - Action Potentials/physiology
KW - Muscles
KW - Neurons/physiology
KW - Optogenetics/methods
U2 - 10.1038/s41467-023-37622-6
DO - 10.1038/s41467-023-37622-6
M3 - SCORING: Journal article
C2 - 37024493
VL - 14
SP - 1939
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -