Functional states shape the spatiotemporal representation of local and cortex-wide neural activity in mouse sensory cortex

The spatiotemporal representation of neural activity during rest and upon sensory stimulation in cortical areas is highly dynamic and may be predominantly governed by cortical state. On the mesoscale level, intrinsic neuronal activity ranges from a persistent state, generally associated with a sustained depolarization of neurons, to a bimodal, slow wave-like state with bursts of neuronal activation alternating with silent periods. These different activity states are prevalent under certain types of sedatives or are associated with spe-cific behavioral or vigilance conditions. Neurophysiological experiments assessing circuit activity usually assume a constant underlying state, yet reports of variability of neuronal responses under seemingly constant conditions are common in the field. Even when a cer-tain type of neural activity or cortical state can be stably maintained over time, the associated response properties are highly relevant for explaining experimental outcomes. Here we describe the spatiotemporal characteristics of ongoing activity and sensory-evoked responses under two predominant functional states in the sensory cortices of mice: persistent activity (PA) and slow wave activity (SWA). Using electrophysiological recordings and local and wide -field calcium recordings, we examine whether spontaneous and sen-sory-evoked neuronal activity propagate throughout the cortex in a state-dependent manner. We find that PA and SWA differ in their spatiotemporal characteristics, which determine the cortical network's response to a sensory stimulus. During PA state, sensory stimu-lation elicits gamma-based short-latency responses that precisely follow each stimulation pulse and are prone to adaptation upon higher stimulation frequencies. Sensory responses during SWA are more variable, dependent on refractory periods following sponta-neous slow waves. Although spontaneous slow waves propagated in anterior-posterior direction in a majority of observations, the direction of propagation of stimulus-elicited wave depends on the sensory modality. These findings suggest that cortical state explains variance and should be considered when investigating multiscale correlates of functional neurocircuit activity.NEW & NOTEWORTHY Here we dissect the cortical representation of brain states based on local photometry recordings and on mesoscale cortical calcium imaging, complemented by electrophysiological recordings in mice. We identify two distinct func-tional states in the sensory cortices, which differ in their spatiotemporal characteristics on the local and global cortical scales. We examine how intrinsic and stimulus-evoked neuronal activity propagates throughout the cortex in a state-dependent manner, supporting the notion that cortical state is a relevant variable to consider for a wide range of neurophysiological experiments.