Spatiotemporal patterns of population response in the visual cortex under isoflurane: from wakefulness to loss of consciousness

Anesthetic drugs are widely used in medicine and research to mediate loss of consciousness (LOC). Isof lurane is a commonly used anesthetic drug; however, its effects on cortical sensory processing, in particular around LOC, are not well understood. Using voltage-sensitive dye imaging, we measured visually evoked neuronal population response from the visual cortex in awake and anesthetized mice at 3 increasing concentrations of isof lurane, thus controlling the level of anesthesia from wakefulness to deep anesthesia. At low concentration of isof lurane, the effects on neuronal measures were minor relative to the awake condition. These effects augmented with increasing isof lurane concentration, while around LOC point, they showed abrupt and nonlinear changes. At the network level, we found that isof lurane decreased the stimulus-evoked intra-areal spatial spread of local neural activation, previously reported to be mediated by horizontal connections, and also reduced intra-areal synchronization of neuronal population. The synchronization between different visual areas decreased with higher isof lurane levels. Isof lurane reduced the population response amplitude and prolonged their latencies while higher visual areas showed increased vulnerability to isof lurane concentration. Our results uncover the changes in neural activity and synchronization at isof lurane concentrations leading to LOC and suggest reverse hierarchical shutdown of cortical areas.