What is cellular voltage imaging?
This novel fluorescence imaging technique uses genetically encoded voltage indicators (GEVIs) that are expressed in neurons. GEVI (e.g. Archon, ASAP3, JEDI-2P, ArcLight) are packaged in viruses such that GEVI sequence is integrated in the neuron’s genome. The fluorescent proteins are then produced and integrated in the neuron’s membrane and they have a key property: their fluorescence behavior is voltage-dependent. That means that photons the protein emits when excited depends, preferably linearly, on the membrane voltage. Therefore, the amount of recorded emitted photons by the GEVI provide information about the membrane voltage. This includes the subthreshold as well as suprathreshold (action potentials) part of the membrane potential, which were previously only accessible via patch-clamp electrophysiology.
Can cellular voltage imaging be used to study neural circuits in awake behaving animals?
While a few years ago most GEVI were largely limited for in-vitro applications, the development of novel and powerful GEVI has allowed their application in dense neural tissues of behaving animals. Critical for this achievement was the development of robotic-assisted evolutionary selection of potent GEVI, sparse-labeling techniques (e.g. soma-targeting) and development of fast (kilohertz) and sensitive optical 1photon and 2photon imaging techniques.
Contributions to voltage imaging techniques
Patterned voltage imaging using digital-mirror-device (DMD). By splitting the laser lights using the DMD into small ‚beamlets‘ targeting selectively neurons‘ somas, the number of neurons recorded and signal-to-noise ratio were remarkably improved.
Ultra-fast voltage imaging. Using a high-performance sCMOS camera, I reccorded single and complex spikes of hippocampal CA1 neurons at 10kHz in awake mice.
