Pan-cortical 2-photon mesoscopic imaging and neurobehavioral alignment in awake, behaving mice

Abstract

The flow of neural activity across the neocortex during active sensory discrimination is constrained by task-specific cognitive demands, movements, and internal states. During behavior, the brain appears to sample from a broad repertoire of activation motifs. Understanding how these patterns of local and global activity are selected in relation to both spontaneous and task-dependent behavior requires in-depth study of densely sampled activity at single neuron resolution across large regions of cortex. In a significant advance toward this goal, we developed procedures to record mesoscale 2-photon Ca2+ imaging data from two novel in vivo preparations that, between them, allow simultaneous access to nearly all of the mouse dorsal and lateral neocortex. As a proof of principle, we aligned neural activity with both behavioral primitives and high-level motifs to reveal the existence of large populations of neurons that coordinated their activity across cortical areas with spontaneous changes in movement and/or arousal. The methods we detail here facilitate the identification and exploration of widespread, spatially heterogeneous neural ensembles whose activity is related to diverse aspects of behavior.

Decision-making dynamics are predicted by arousal and uninstructed movements

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Modulation of metastable ensemble dynamics explains optimal coding at moderate arousal in auditory cortex

“…Mice were allowed to recover for three days in an incubator recovery chamber. A more detailed procedure can be found in [22, 85].…”