Elucidating a locus coeruleus-dentate gyrus dopamine pathway for operant reinforcement

Abstract
Data availability
Article and author information
Metrics

Abstract

Animals can learn to repeat behaviors to earn desired rewards, a process commonly known as reinforcement learning. While previous work has implicated the ascending dopaminergic projections to the basal ganglia in reinforcement learning, little is known about the role of the hippocampus. Here we report that a specific population of hippocampal neurons and their dopaminergic innervation contribute to operant self-stimulation. These neurons are located in the dentate gyrus, receive dopaminergic projections from the locus coeruleus, and express D1 dopamine receptors. Activation of D1+ dentate neurons is sufficient for self-stimulation: mice will press a lever to earn optogenetic activation of these neurons. A similar effect is also observed with selective activation of the locus coeruleus projections to the dentate gyrus, and blocked by D1 receptor antagonism. Calcium imaging of D1+ dentate neurons revealed significant activity at the time of action selection, but not during passive reward delivery. These results reveal the role of dopaminergic innervation of the dentate gyrus in supporting operant reinforcement.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

Elijah A Petter

Department of Psychology and Neuroscience, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.
Isabella P Fallon

Department of Psychology and Neuroscience, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.
Ryan N Hughes

Department of Psychology and Neuroscience, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-4999-0215
Glenn DR Watson

Department of Psychology and Neuroscience, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.
Warren H Meck

Department of Psychology and Neuroscience, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.
Francesco Paolo Ulloa Severino

Department of Psychology and Neuroscience, Duke University, Durham, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-3725-9713
Henry H Yin

Department of Psychology and Neuroscience, Duke University, Durham, United States

For correspondence
hy43@duke.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-1546-6850

Funding

National Institute on Drug Abuse (DA040701)

Henry H Yin

National Institute of Neurological Disorders and Stroke (NS094754)

Henry H Yin

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 experimental procedures were conducted in accordance with standard ethical guidelines and were approved by the Duke University Institutional Animal Care and Use Committee (protocol number: 162-22-09).

Copyright

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.