Cell Reports (Oct 2024)

Cortical acetylcholine dynamics are predicted by cholinergic axon activity and behavior state

  • Erin Neyhart,
  • Na Zhou,
  • Brandon R. Munn,
  • Robert G. Law,
  • Cameron Smith,
  • Zakir H. Mridha,
  • Francisco A. Blanco,
  • Guochuan Li,
  • Yulong Li,
  • Ming Hu,
  • Matthew J. McGinley,
  • James M. Shine,
  • Jacob Reimer

Journal volume & issue
Vol. 43, no. 10
p. 114808

Abstract

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Summary: Acetylcholine (ACh) is thought to play a role in driving the rapid, spontaneous brain-state transitions that occur during wakefulness; however, the spatiotemporal properties of cortical ACh activity during these state changes are still unclear. We perform simultaneous imaging of GRAB-ACh sensors, GCaMP-expressing basal forebrain axons, and behavior to address this question. We observed a high correlation between axon and GRAB-ACh activity around periods of locomotion and pupil dilation. GRAB-ACh fluorescence could be accurately predicted from axonal activity alone, and local ACh activity decreased at farther distances from an axon. Deconvolution of GRAB-ACh traces allowed us to account for sensor kinetics and emphasized rapid clearance of small ACh transients. We trained a model to predict ACh from pupil size and running speed, which generalized well to unseen data. These results contribute to a growing understanding of the precise timing and spatial characteristics of cortical ACh during fast brain-state transitions.

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