Probing the time scales of perceptual readout with white noise optogenetic inhibition

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Project Abstract During visually guided behaviors, only hundreds of milliseconds elapse between a sensory stimulus and its ensuing action, yet spiking responses across sensorimotor circuits come to represent stimulus features and guide forthcoming actions. Owing to the immense complexity of brain circuits, there is great uncertainty as to which spikes (and in which brain areas) causally contribute to behavior. We need methods capable of resolving how moment-to-moment fluctuations in spiking drive perception and action. A versatile tool for examining relationships between sensory input and spiking or behavior is white noise analysis. A random, dynamic stimulus is presented and these fluctuations can be leveraged to generate unbiased estimates of the stimulus features that drive neuronal spiking (spike-triggered average) or the periods of sensory input that drive perceptual decisions (psychophysical kernel). We have adapted white noise analysis for optogenetic stimulation. We deliver random patterns of weak optogenetic inhibition to visual areas during behavior and calculate the average optogenetic signal associated with perceptual reports (hits, misses). Our preliminary data show that white noise optogenetic inhibition rapidly yields kernels that define the contribution of spiking in specific neuronal populations to specific behaviors, with a resolution of a tens of milliseconds (optogenetic behavioral kernel, OBK). Such precise timing information would be impractical to obtain with standard optogenetic approaches (e.g., pulses or sustained inhibition). We will validate and apply this approach by determining how OBKs measured in lower and higher visual areas depend on visual input and task demands, and in doing so generate new observations that link patterns of spiking with perceptual decisions throughout the visual brain. Mice will be trained to work reliably at threshold in perceptual tasks. In the first experiment, visual information will arrive suddenly (super-threshold intensity, contrast steps) or gradually (near-threshold, contrast ramps) and we will relate OBKs to changes in the distributions of stimulus-evoked spikes. In the second experiment, mice will be required to respond to a target orientation and reject distractors. We will measure OBKs in both cortical (striate and extrastriate visual areas) and subcortical (superior colliculus) visual areas to determine the time course of their respective contributions to task performance. A subset of mice will also be implanted with fixed-wire optrodes to facilitate concurrent electrophysiological recordings and optogenetic perturbations during behavior. These data will relate moment-to-moment reductions in stimulus and/or task-evoked spikes with perceptual reports and enable comparisons between population spiking and OBKs. This work will provide unprecedented resolution into the periods of neuronal activity in cortical and subcortical visual pathways that causally contribute to perception and behavior. Our experiments will establish a powerful method for constructing kernels that relate spiking dynamics in different visual areas to visually- guided behaviors, a method that could find wide application among systems neuroscientists.