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
Affiliations
Erin Neyhart
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA
Na Zhou
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA
Brandon R. Munn
Brain and Mind Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia; Complex Systems Group, School of Physics, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia
Robert G. Law
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA
Cameron Smith
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA
Zakir H. Mridha
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA
Francisco A. Blanco
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA
Guochuan Li
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU–IDG/McGovern Institute for Brain Research, Beijing 100871, China; Peking–Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
Yulong Li
State Key Laboratory of Membrane Biology, Peking University School of Life Sciences, Beijing 100871, China; PKU–IDG/McGovern Institute for Brain Research, Beijing 100871, China; Peking–Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China
Ming Hu
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA
Matthew J. McGinley
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA
James M. Shine
Brain and Mind Centre, School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia; Complex Systems Group, School of Physics, Faculty of Science, The University of Sydney, Sydney, NSW 2006, Australia
Jacob Reimer
Neuroscience Department, Baylor College of Medicine, Houston, TX 77030, USA; Corresponding author
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.
