Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency
- Yale University, United States
- NIH, United States
- Chinese Institute for Brain Research, China
- Peiking University, China
- Yale University School of Medicine, United States
Abstract
The basolateral amygdala (BLA) is critical for associating initially neutral cues with appetitive and aversive stimuli and receives dense neuromodulatory acetylcholine (ACh) projections. We measured BLA ACh signaling and activity of neurons expressing CaMKIIα (a marker for glutamatergic principal cells) in mice during cue-reward learning using a fluorescent ACh sensor and calcium indicators. We found that ACh levels and nucleus basalis of Meynert (NBM) cholinergic terminal activity in the BLA (NBM-BLA) increased sharply in response to reward-related events and shifted as mice learned the cue-reward contingency. BLA CaMKIIα neuron activity followed reward retrieval and moved to the reward-predictive cue after task acquisition. Optical stimulation of cholinergic NBM-BLA terminal fibers led to quicker acquisition of the cue-reward contingency. These results indicate BLA ACh signaling carries important information about salient events in cue-reward learning and provides a framework for understanding how ACh signaling contributes to shaping BLA responses to emotional stimuli.
Data availability
All data generated or analysed during this study are included in the manuscript and supporting files. Source data files have been provided for all experiments on Dryad Digital Repository: doi:10.5061/dryad.3xsj3txcf
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Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingencyDryad Digital Repository, doi:10.5061/dryad.3xsj3txcf.
Article and author information
Author details
Rufina Kamaletdinova
Prithviraj Rajebhosale
Marina R Picciotto
Funding
National Institute on Drug Abuse (DA14241)
- Richard B Crouse
- Kristen Kim
- Hannah M Batchelor
- Rufina Kamaletdinova
- Justin Chan
- Steven T Pittenger
- Yann S Mineur
- Marina R Picciotto
National Institute on Drug Abuse (DA037566)
- Richard B Crouse
- Kristen Kim
- Hannah M Batchelor
- Rufina Kamaletdinova
- Justin Chan
- Steven T Pittenger
- Yann S Mineur
- Marina R Picciotto
National Institute of Mental Health (MH077681)
- Richard B Crouse
- Kristen Kim
- Hannah M Batchelor
- Rufina Kamaletdinova
- Justin Chan
- Steven T Pittenger
- Yann S Mineur
- Marina R Picciotto
National Institute of Neurological Disorders and Stroke (NS022061)
- Prithviraj Rajebhosale
- Lorna W Role
- David A Talmage
National Institute of Mental Health (MH109104)
- Prithviraj Rajebhosale
- Lorna W Role
- David A Talmage
National Institute on Drug Abuse (DA046160)
- Xiao-Bing Gao
National Institute of Neurological Disorders and Stroke (Intramural)
- Prithviraj Rajebhosale
- Lorna W Role
National Institute of Mental Health (Intramural)
- Prithviraj Rajebhosale
- David A Talmage
National Institute of Neurological Disorders and Stroke (T32-NS007224)
- Richard B Crouse
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 Yale University Institutional Animal Care & Use Committee in compliance with the National Institute of Health's Guide for the Care and Use of Laboratory Animals. (protocol: 2019-07895)
Reviewing Editor
- Matthew N Hill, University of Calgary, Canada
Version history
- Received: March 27, 2020
- Accepted: September 17, 2020
- Accepted Manuscript published: September 18, 2020 (version 1)
- Accepted Manuscript updated: September 22, 2020 (version 2)
- Version of Record published: October 1, 2020 (version 3)
Copyright
This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
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Acetylcholine is released in the basolateral amygdala in response to predictors of reward and enhances learning of cue-reward contingency
eLife 9:e57335.
https://doi.org/10.7554/eLife.57335
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