Elucidating a locus coeruleus-dentate gyrus dopamine pathway for operant reinforcement
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.
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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
© 2023, Petter 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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Further reading
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- Neuroscience
Spiny projection neurons (SPNs) in dorsal striatum are often proposed as a locus of reinforcement learning in the basal ganglia. Here, we identify and resolve a fundamental inconsistency between striatal reinforcement learning models and known SPN synaptic plasticity rules. Direct-pathway (dSPN) and indirect-pathway (iSPN) neurons, which promote and suppress actions, respectively, exhibit synaptic plasticity that reinforces activity associated with elevated or suppressed dopamine release. We show that iSPN plasticity prevents successful learning, as it reinforces activity patterns associated with negative outcomes. However, this pathological behavior is reversed if functionally opponent dSPNs and iSPNs, which promote and suppress the current behavior, are simultaneously activated by efferent input following action selection. This prediction is supported by striatal recordings and contrasts with prior models of SPN representations. In our model, learning and action selection signals can be multiplexed without interference, enabling learning algorithms beyond those of standard temporal difference models.
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