All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals
30 May 2023. Identifying connections between distinct neurons and their contribution to driving behaviour is a central issue in neuroscience. To explore such relations, methods to record and concurrently regulate neural activity are needed. 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. A team of scientists now managed to develop an optogenetic voltage-clamp (OVC).
Their 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.
They established the optogenetic voltage-clamp in muscles and neurons of the worm 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 optogenetic voltage-clamp reports on homeostatically altered cellular physiology in mutants and on Ca-channel properties, and can dynamically clamp spiking in C. elegans.
Combining non-invasive imaging with control capabilities of electrophysiology, the optogenetic voltage-clamp facilitates high-throughput, contact-less electrophysiology in individual cells and paves the way for true optogenetic control in behaving animals.
Contact:
Alexander Gottschalk, Buchmann Institute for Molecular Life Sciences and Institute of Biophysical Chemistry, Goethe University, Frankfurt/M., a.gottschalk@em.uni-frankfurt.de
Research publication:
Amelie C. F. Bergs, Jana F. Liewald, Silvia Rodriguez-Rozada, Qiang Liu, Christin Wirt, Artur Bessel, Nadja Zeitzschel, Hilal Durmaz, Adrianna Nozownik, Holger Dill, Maëlle Jospin, Johannes Vierock, Cornelia I. Bargmann, Peter Hegemann, J. Simon Wiegert, Alexander Gottschalk. 2023. All-optical closed-loop voltage clamp for precise control of muscles and neurons in live animals. Nature Communications 14, 1939. https://doi.org/10.1038/s41467-023-37622-6