Cortical acetylcholine dynamics are predicted by cholinergic axon activity and behavior state
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.
Authors
- Na Zhou (ORCID: https://orcid.org/0000-0002-7099-1351)
- Guochuan Li (ORCID: https://orcid.org/0009-0000-6837-9780)
- Francisco A. Blanco (ORCID: https://orcid.org/0000-0002-1228-8625)
- Brandon Munn (ORCID: https://orcid.org/0000-0002-3638-1605)
- James M. Shine (ORCID: https://orcid.org/0000-0003-1762-5499)
- Zakir Mridha (ORCID: https://orcid.org/0000-0002-9772-9812)
- Cameron Smith (ORCID: https://orcid.org/0000-0002-2079-4667)
- Erin Neyhart (ORCID: https://orcid.org/0000-0001-9164-0553)
- Robert Law (ORCID: https://orcid.org/0000-0002-1220-3871)
- Jacob Reimer (ORCID: https://orcid.org/0000-0003-4364-8846)
- Matthew J. McGinley (ORCID: https://orcid.org/0000-0002-6516-9670)
- Yulong Li (ORCID: https://orcid.org/0000-0002-9166-9919)
- Ming Hu
Institutions
- The University of Sydney (AU)
- Baylor College of Medicine (US)
- Peking University (CN)
- Chinese Institute for Brain Research (CN)
- Center for Life Sciences (CN)
Publication Details
- Journal
- Cell Reports
- Published
- 2024-10-01
- DOI
- https://doi.org/10.1016/j.celrep.2024.114808
- Citations
- 12
- Primary Topic
- Photoreceptor and optogenetics research
- Type
- article
- Field-Weighted Citation Impact
- 3.22
Funders
- National Institutes of Health
- Medical Research Council
- National Health and Medical Research Council
- National Science Fund for Distinguished Young Scholars
- National Institute on Deafness and Other Communication Disorders
- National Institute of Diabetes and Digestive and Kidney Diseases
- Office of Research on Women's Health