Kavli Affiliate: Cori Bargmann
| Authors: Amelie CF Bergs, Jana F Liewald, Silvia Rodriguez-Rozada, Qiang Liu, Christin Wirt, Artur Bessel, Nadja Zeitzschel, Hilal Durmaz, Adrianna Nozownik, Johannes Vierock, Cori Bargmann, Peter Hegemann, J. Simon Wiegert and Alexander Gottschalk
| Summary:
Optogenetics are used to stimulate or inhibit neurons. Because optogenetic stimulation is typically static, neurons and circuits can quickly adapt, allowing perturbation, but not true control. To overcome this, we established an optogenetic voltage-clamp (OVC). The genetically encoded 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 at a distinct potential. We established the OVC in muscles and neurons of Caenorhabditis elegans, and transferred it to hippocampal neurons in rat brain slices. We calibrated fluorescence signals to electrically measured membrane potentials, showed that the OVC reports on homeostatically altered cellular physiology in mutants affecting neurotransmission, and that it can dynamically clamp spiking. The OVC combines non-invasive imaging with the control capabilities of electrophysiology. Its applicability to individual cells facilitates high-throughput contact-less electrophysiology and paves the way for true optogenetic control in behaving animals.