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Central neurons operate in a regime of constantly fluctuating conductances,induced by thousands of presynaptic cells. Channelrhodopsins have been almostexclusively used to imprint a fixed spike pattern by sequences of briefdepolarizations. Here we introduce continuous dynamic photostimulation(CoDyPs), a novel approach to mimic in-vivo like input fluctuationsnoninvasively in cells transfected with the weakly inactivatingchannelrhodopsin variant ChIEF. Even during long-term experiments, culturedneurons subjected to CoDyPs generate seemingly random, but reproducible spikepatterns. In voltage clamped cells CoDyPs induced highly reproducible currentwaveforms that could be precisely predicted from the light-conductance transferfunction of ChIEF. CoDyPs can replace the conventional, flash-evoked imprintingof spike patterns in in-vivo and in-vitro studies, preserving natural activity.When combined with non-invasive spike-detection, CoDyPs allows the acquisitionof order of magnitudes larger data sets than previously possible, for studiesof dynamical response properties of many individual neurons.

Continuous Dynamic Photostimulation - inducing in-vivo-like fluctuating conductances with Channelrhodopsins