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
-
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.
Reviewing Editor
- Matthew N Hill, University of Calgary, Canada
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)
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.
Metrics
-
- 6,723
- views
-
- 806
- downloads
-
- 56
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
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
Further reading
-
- Genetics and Genomics
- Neuroscience
Single-cell RNA sequencing reveals the extent to which marmosets carry genetically distinct cells from their siblings.
-
- Neuroscience
We are unresponsive during slow-wave sleep but continue monitoring external events for survival. Our brain wakens us when danger is imminent. If events are non-threatening, our brain might store them for later consideration to improve decision-making. To test this hypothesis, we examined whether novel vocabulary consisting of simultaneously played pseudowords and translation words are encoded/stored during sleep, and which neural-electrical events facilitate encoding/storage. An algorithm for brain-state-dependent stimulation selectively targeted word pairs to slow-wave peaks or troughs. Retrieval tests were given 12 and 36 hr later. These tests required decisions regarding the semantic category of previously sleep-played pseudowords. The sleep-played vocabulary influenced awake decision-making 36 hr later, if targeted to troughs. The words’ linguistic processing raised neural complexity. The words’ semantic-associative encoding was supported by increased theta power during the ensuing peak. Fast-spindle power ramped up during a second peak likely aiding consolidation. Hence, new vocabulary played during slow-wave sleep was stored and influenced decision-making days later.
