Cortical Acetylcholine Dynamics Are Predicted by Cholinergic Axon Activity and Behavior State

Authors

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

Publication Date

10-22-2024

Journal

Cell Reports

DOI

10.1016/j.celrep.2024.114808

PMID

39383037

PMCID

PMC11755675

PubMedCentral® Posted Date

1-23-2025

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Acetylcholine, Animals, Axons, Cholinergic Neurons, Mice, Cerebral Cortex, Male, Behavior, Animal

Abstract

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.