A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes
- Massachusetts Eye and Ear Infirmary, United States
- Massachusetts General Hospital, United States
- Chinese Institute for Brain Research, China
- Peiking University School of Life Sciences, China
Abstract
Basal forebrain cholinergic neurons (BFCNs) project throughout the cortex to regulate arousal, stimulus salience, plasticity, and learning. Although often treated as a monolithic structure, the basal forebrain features distinct connectivity along its rostrocaudal axis that could impart regional differences in BFCN processing. Here, we performed simultaneous bulk calcium imaging from rostral and caudal BFCNs over a one-month period of variable reinforcement learning in mice. BFCNs in both regions showed equivalently weak responses to unconditioned visual stimuli and anticipated rewards. Rostral BFCNs in the horizontal limb of the diagonal band were more responsive to reward omission, more accurately classified behavioral outcomes, and more closely tracked fluctuations in pupil-indexed global brain state. Caudal tail BFCNs in globus pallidus and substantia innominata were more responsive to unconditioned auditory stimuli, orofacial movements, aversive reinforcement, and showed robust associative plasticity for punishment-predicting cues. These results identify a functional topography that diversifies cholinergic modulatory signals broadcast to downstream brain regions.
Data availability
Figure 1 - Source Data 1 contains the data for Figure 1D. All data generated or analyzed during this study are available on Mendeley Data (doi:10.17632/d8tjdxyjcm.2)
Article and author information
Author details
Funding
National Institute on Deafness and Other Communication Disorders (DC017078)
- Daniel B Polley
The Nancy Lurie Marks Family Foundation
- Daniel B Polley
Herchel Smith Harvard Scholarship
- Blaise Robert
Fondation Zdenek et Michaela Bakala Scholarship
- Blaise Robert
National Institute of Mental Health (K08MH116135)
- Eyal Y Kimchi
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Martin Vinck, Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Germany
Ethics
Animal experimentation: All procedures were approved by the Massachusetts Eye and Ear Animal Care and Use Committee (protocol #10-03-006A) and followed the guidelines established by the National Institutes of Health for the care and use of laboratory animals.
Version history
- Preprint posted: April 19, 2019 (view preprint)
- Received: April 17, 2021
- Accepted: November 16, 2021
- Accepted Manuscript published: November 25, 2021 (version 1)
- Version of Record published: December 8, 2021 (version 2)
Copyright
© 2021, Robert et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes
eLife 10:e69514.
https://doi.org/10.7554/eLife.69514
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