A functional topography within the cholinergic basal forebrain for encoding sensory cues and behavioral reinforcement outcomes

  1. Blaise Robert
  2. Eyal Y Kimchi
  3. Yurika Watanabe
  4. Tatenda Chakoma
  5. Miao Jing
  6. Yulong Li
  7. Daniel B Polley  Is a corresponding author
  1. Massachusetts Eye and Ear Infirmary, United States
  2. Massachusetts General Hospital, United States
  3. Chinese Institute for Brain Research, China
  4. 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)

The following data sets were generated

Article and author information

Author details

  1. Blaise Robert

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-7945-8775
  2. Eyal Y Kimchi

    Department of Neurology, Massachusetts General Hospital, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Yurika Watanabe

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Tatenda Chakoma

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Miao Jing

    Chinese Institute for Brain Research, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  6. Yulong Li

    State Key Laboratory of Membrane Biology, Peiking University School of Life Sciences, Beijing, China
    Competing interests
    The authors declare that no competing interests exist.
  7. Daniel B Polley

    Eaton-Peabody Laboratories, Massachusetts Eye and Ear Infirmary, Boston, United States
    For correspondence
    Daniel_Polley@meei.harvard.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5120-2409

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.

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.

Reviewing Editor

  1. Martin Vinck, Ernst Strüngmann Institute (ESI) for Neuroscience in Cooperation with Max Planck Society, Germany

Version history

  1. Preprint posted: April 19, 2019 (view preprint)
  2. Received: April 17, 2021
  3. Accepted: November 16, 2021
  4. Accepted Manuscript published: November 25, 2021 (version 1)
  5. 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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  1. Blaise Robert
  2. Eyal Y Kimchi
  3. Yurika Watanabe
  4. Tatenda Chakoma
  5. Miao Jing
  6. Yulong Li
  7. Daniel B Polley
(2021)
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

Share this article

https://doi.org/10.7554/eLife.69514

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