Perceptual Weighting of V1 Spikes Revealed by Optogenetic White Noise Stimulation

During visually guided behaviors, mere hundreds of milliseconds can elapse between a sensory input and its associated behavioral response. How spikes occurring at different times are integrated to drive perception and action remains poorly understood. We delivered random trains of optogenetic stimulation (white noise) to excite inhibitory interneurons in V1 of mice while they performed a visual detection task. We then performed a reverse correlation analysis on the optogenetic stimuli to generate a neuronal-behavioral kernel: an unbiased, temporally-precise estimate of how suppression of V1 spiking at different moments around the onset of a visual stimulus affects detection of that stimulus. Electrophysiological recordings enabled us to capture the effects of optogenetic stimuli on V1 responsivity and revealed that the earliest stimulus-evoked spikes are preferentially weighted for guiding behavior. These data demonstrate that white noise optogenetic stimulation is a powerful tool for understanding how patterns of spiking in neuronal populations are decoded in generating perception and action. Significance Statement How the brain decodes dynamic neuronal responses to generate perception and behavior remains uncertain. A critical challenge is determining the relative contribution of spikes that occur at different times on the timescale of brain computations (tens of ms). Optogenetic tools permit causal investigations into neuronal-behavioral relationships, but are generally impractical for obtaining millisecond resolution. We circumvented this by delivering random (white noise) patterns of optogenetic inhibition to the primary visual cortex of behaving mice during visual tasks. Aligning optogenetic stimuli to task outcomes (hit, miss) yielded a neuronal-behavioral kernel – a temporal weighting that describes how inhibition at different moments impacts perception of visual stimuli. Thus, this method is a powerful tool for linking neuronal spiking, perception, and behavior.