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

Elife. 2024 May 29:13:RP94167. doi: 10.7554/eLife.94167.

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 for simultaneous access to nearly all 0f 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.

Keywords: 2-photon; behavior; calcium imaging; cortex; in vivo; mesoscope; mouse; neuroscience.

MeSH terms

  • Animals
  • Behavior, Animal* / physiology
  • Calcium / metabolism
  • Male
  • Mice
  • Microscopy, Fluorescence, Multiphoton / methods
  • Neocortex / diagnostic imaging
  • Neocortex / physiology
  • Neurons* / physiology
  • Wakefulness* / physiology

Substances

  • Calcium