  To understand sensory processing in neuronal populations, it is necessary to
deliver stimuli to the sensory organs of animals and record evoked population
activity downstream. However, the pathways from sensory input to synaptic
currents in cells that are several synapses removed from sensory organs are
complex. Intrinsic noise and uncontrolled modulatory input from other brain
regions can interfere with the delivery of well-defined stimuli. Here we
investigate the ability of channelrhodopsins to deliver precise time-varying
currents to neurons at any point along the sensory-motor pathway. To do this,
we first deduce the amplitude response function of channelrhodopsin-2 (ChR2)
using a three state Markov model of channel kinetics. With biophysically
realistic parameters, this function supports a relatively broad signal passband
and contains a resonance. We confirm the validity of our predicted amplitude
response function using time-varying optical stimulation of excitatory neurons
that express either wild type ChR2 or the ChR2(H134R) mutant. Together, our
results indicate that ChR2-derived optogenetic tools are useful for delivering
repeatable, time-varying currents to genetically-specified populations over a
physiologically-relevant frequency band.
